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Back to Journal »Diabetes, Metabolic Syndrome and Obesity: Goals and Treatment» Volume 14
Astragalus-saffron-rhubarb mixture delays the progression of diabetic nephropathy in db/db mice
Authors: Zhou Xiaochun, Liang Yujie, Qin L, Wei GH, Wang Jingqing
Published on December 1, 2021, Volume 2021: 14 pages 4679-4690
DOI https://doi.org/10.2147/DMSO.S334662
Single anonymous peer review
Approved for publication editor: Professor Minghui Zou
Zhou Xiaochun, Liang Yaojun, Qin Long, Wei Guohua, Department of Nephrology Wang Jianqin, Second Hospital of Lanzhou University, Lanzhou, 730030 Corresponding author: Department of Nephrology Wang Jianqin, Lanzhou, Second University Hospital, No. 82 Cuiyingmen, Chengguan District, Lanzhou City 730030 Tel: +8613919038189 Email protected] Purpose: This study aims to investigate the effect of astragalus-saffron-rhubarb mixture (bao'shen recipe, BSR) on diabetic nephropathy (DN) in db/db mice, and to preliminarily explore its possible underlying mechanism. Methods: 125 8-week-old DN male db/db mice were randomly divided into 5 groups: model group, irbesartan group and high, medium and low dose BSR group, 25 male db/m mice. Used as a blank control. Animals were sacrificed at 8, 12, 16, 20, and 24 weeks of feeding, and blood and urine samples were collected. Blood glucose, urea nitrogen, creatinine, and urinary albumin excretion rate (UAER) were measured by a blood glucose meter with corresponding test kits. The kidney tissue of each mouse was stained with hematoxylin and eosin (H&E), Masson, and periodic acid Schiff (PAS). Renal homogenate enzyme-linked immunosorbent assay was used to detect IL-6, TNF-α, TNF-1R and TNF-2R. In addition, statistical analysis is performed on the obtained data through one-way analysis of variance. Results: BSR can effectively reduce body weight, blood sugar, UAER, blood urea nitrogen, creatinine levels, reduce mesangial tissue proliferation, and reduce IL-6, TNF-α, TNF-1R, and TNF-2R levels. In the kidney tissue of db/db mice with DN. It is worth noting that the high-dose BSR treatment group is better than the irbesartan treatment group in improving the above aspects. Conclusion: BSR can effectively delay the progression of DN, partly related to its anti-inflammatory effect. [Keywords]: Chinese medicine for treating inflammatory factors in diabetic nephropathy
Diabetic nephropathy (DN) is the most common and serious chronic complication of diabetes. In developed countries, DN has become the main reason for renal replacement therapy in patients with end-stage renal failure (ESRF)1. Diabetes is expected to become a major disease in developing countries in the next 20 years. Approximately 25-40% of type 2 diabetes (T2DM) patients have kidney damage and chronic kidney disease. 2,3 DN has a variety of pathophysiological mechanisms, including microvascular, macrovascular changes, glucose and lipid metabolism disorders, oxidative stress, inflammation, fibrosis, coagulation and other factors that play an important role in the progression of DN. 4-8 Even so, the exact mechanism of DN is still not fully understood. Aiming at the pathogenesis of DN, comprehensive treatment can make blood glucose, blood lipids, blood pressure and other indicators reach the standard. These treatments can only delay the pathological progress of diabetes, but cannot reduce the incidence of diabetes. ESRD in patients with DN. 4 Therefore, finding new treatments is the key to the prevention and treatment of DN.
Traditional Chinese medicine plays an important role in the prevention and treatment of chronic kidney disease and T2DM in China, which is proven by a number of pharmacological and clinical studies. 9-12 Previous reports indicate that astragalus, saffron and rhubarb are drugs commonly used for diabetes and chronic kidney disease. 13-15 indicate that mixing the above three drugs in an appropriate ratio may have a protective effect on DN. However, the above three drugs are currently mainly administered in the form of a single drug, and there is little information about mixing them into a Chinese herbal compound for the treatment of DN. In this context, we previously combined the above-mentioned drugs in appropriate proportions into astragalus-saffron-rhubarb mixture, named Baoshen Fang, for patients with chronic renal failure. In addition, we found that BSR can prevent the progression of DN by reducing the expression of CTGF in DN rats and increasing the expression of MMP-9. 16
Based on this, this study aims to further explore the protective effect of BSR on the kidneys of db/db DN mice and its influence on renal tissue inflammatory cytokines related to the progression of DN, including interleukin 6 (IL-6). ), tumor necrosis factor-α (TNF-α), tumor necrosis factor α receptor-1 (TNF-1R) and tumor necrosis factor-α receptor 2 (TNF-2R).
Astragalus, rhubarb, and saffron were purchased from Lanzhou Huanghe Pharmaceutical Co., Ltd., and the BSR composition was: astragalus 60g, rhubarb 12g, and saffron 6g. Soak the above three medicines in pure water for 30 minutes, boil on high heat, and simmer for 30 minutes. After filtering through four layers of gauze, the BSR is concentrated to 2.235 g/mL and placed in a refrigerator at -20°C for later use.
Animal maintenance and experimental procedures were carried out in accordance with the National Institutes of Health's Laboratory Animal Use Guidelines, and were approved by the Animal Care Committee of the Second Hospital of Lanzhou University (Lanzhou, China). 125 male db/db diabetic mice and non-diabetic littermate control db/m mice (n = 25) in the C57BL/6 background were from Nanjing Model Animal Research Institute. The mice were kept in a room with a constant temperature of 22±2°C, and the light/dark cycle was 12 hours.
These 6-week-old male db/db mice and db/m mice were first adaptively reared for 2 weeks, and then randomly divided into 5 groups, each with 25 animals: control group (distilled water, db/m), model group (distilled water, db/db-m), positive group (irbesartan, 0.05mg/kg, db/db-me), high (3.3525g/kg crude drug, db/db-hd), medium (2.235g/kg crude drug, db/db-md) and low (1.1175g/kg crude drug, db/db-ld) dose of BSR group.
At 0, 4, 8, 12, and 24 weeks, the body weight and FBG level obtained by the blood glucose meter (Sinocare Inc., China) were measured.
Five mice in each group were put to death under anesthesia at the same point and then blood samples were collected. Serum was collected by centrifugation at 3000 rpm at 4°C for 10 minutes. The detection of urea nitrogen and creatinine uses a urea nitrogen detection kit and a creatinine detection kit (Nanjing Jiancheng Institute of Bioengineering, China). A mouse urine microalbuminuria test kit (Shanghai Enzyme Link Biotechnology Co., Ltd., China) was used to detect microalbuminuria.
Weigh the kidney tissue, add 10 mL of tissue lysate (radioimmunoprecipitation test [RIPA]: phenylmethylsulfonyl fluoride [PMSF] ratio is 100:1), and grind with an electronic tissue homogenizer at 4°C for 30 minutes (Shanghai Jingxin Industrial Development Co., Ltd., China). Tissue homogenate was obtained by centrifuging the suspension at 12,000 rpm for 10 minutes (Beckman Coulter, USA, Model: Allegra X-30R), and then detecting IL-6, TNF-α, TNF-1R and TNF-2R ELISA kit [Small Mouse IL-6 (ab100713), Mouse TNF-α ELISA Kit (ab208348), Mouse sTNF-1R ELISA Kit (TNFRSF1A, ab202408), Mouse sTNF-2R ELISA Kit (TNFRSF1b, ab202412), Ab UK ],respectively. All procedures are carried out in strict accordance with the instructions.
The kidney tissue was collected and fixed in 4% phosphate buffered paraformaldehyde. After paraffin embedding, 3 μm thick kidney tissue sections were prepared, deparaffinized in xylene, and rehydrated in graded ethanol. Then, hematoxylin and eosin (H&E), PAS and Masson trichrome stained samples were used for histopathological examination, respectively.
The data was analyzed by SPSS25.0 statistical software. Data with normal distribution and homogeneity of variance are expressed as mean±standard deviation (x±SD), and one-way analysis of variance is used to compare within a group, and t-test is used to compare between the two groups. P <0.05 is considered statistically significant.
The db/db mice were treated with Irbesartan or BSR at the 8th week of modeling. During the treatment, no mice were infected or bitten and died, indicating that the mice tolerated BSR well.
The weight of mice in the blank control group (db/m) did not change significantly during the feeding process (P>0.05). In sharp contrast, the weight of mice in the model group was significantly higher than that of the control group at the 8, 12, 16, 20, and 32 weeks of feeding (all P <0.01). There was no significant difference in body weight between the db/db-me group and the db/db-m group (P> 0.05). It is worth noting that, compared with mice in the db/db-m group, mice treated with high and medium doses of BSR had lower body weights at the same time point (all P <0.01) (both P <0.05). There was no significant change in body weight in the db/db-ld group before and after the medication, and the body weight was the same as that in the db/db-me group at the same time point (all P>0.05), Figure 1). The results showed that both medium and high doses of BSR could reduce the body weight of mice, and the body weight of the positive control group had no significant change. Figure 1 The effect of BSR on the body weight of db/db DN mice. The animals were divided into six groups (n = 25): control group (db/m), model group (db/db-m), positive group (db/db-me) and high BSR (db/db-hd), Medium (db/db-md) and low (db/db-ld) dose groups. The data are shown as mean ± SD.
Figure 1 The effect of BSR on the body weight of db/db DN mice. The animals were divided into six groups (n = 25): control group (db/m), model group (db/db-m), positive group (db/db-me) and high BSR (db/db-hd), Medium (db/db-md) and low (db/db-ld) dose groups. The data are shown as mean ± SD.
During the experiment, the blood glucose level of the db/db-m group was basically stable (P>0.05) compared with that of the db/m group, and the difference was statistically significant. Feeding at 8, 12, 16, 20, and 32 weeks (all P <0.01). High and medium dose BSR intervention can improve the elevated blood glucose levels of mice in the db/db-m group (all P <0.05), and the blood glucose levels of the three groups are lower than those of the db/ db-me group at the same time point (all P <0.01 ). There was no significant change in blood glucose levels in the db/db-ld group before and after the medication, which was not statistically significant compared with the db/db-me group during the same period (P> 0.05, Figure 2). In addition, there was no significant difference in blood glucose levels between the db/db-me group and the db/db-m group (P>0.05). The results show that medium and high doses of BSR have the ability to reduce blood glucose levels in mice. Figure 2 The effect of BSR on blood sugar in db/db DN mice (mmol/L). The animals were divided into six groups (n = 25): control group (db/m), model group (db/db-m), positive group (db/db-me) and high BSR (db/db-hd), Medium (db/db-md) and low (db/db-ld) dose groups. The data are shown as mean ± SD.
Figure 2 The effect of BSR on blood sugar in db/db DN mice (mmol/L). The animals were divided into six groups (n = 25): control group (db/m), model group (db/db-m), positive group (db/db-me) and high BSR (db/db-hd), Medium (db/db-md) and low (db/db-ld) dose groups. The data are shown as mean ± SD.
Similar to the change trend of blood glucose in mice, the UAER of mice in the db/m group did not change significantly during the feeding process (P>0.05). In sharp contrast, compared with the db/m group, the UAER of the db/db-m group was significantly higher after 12 weeks of feeding (P <0.01). Interestingly, the UAER of mice in the db/db-me group and the BSR 3 dose group decreased significantly at 4, 8, 12, and 24 weeks (P <0.01). The UAER of the db-hd group was significantly lower than that of the db/db-me group (P <0.01). There was no significant difference in UAER between the db/db-md group and the db/db-me group (P>0.05, Figure 3). Figure 3 The effect of BSR on the UAER of db/db DN mice (mg/24 hours). The animals were divided into six groups (n = 25): control group (db/m), model group (db/db-m), positive group (db/db-me) and high BSR (db/db-hd), Medium (db/db-md) and low (db/db-ld) dose groups. The data are shown as mean ± SD.
Figure 3 The effect of BSR on the UAER of db/db DN mice (mg/24 hours). The animals were divided into six groups (n = 25): control group (db/m), model group (db/db-m), positive group (db/db-me) and high BSR (db/db-hd), Medium (db/db-md) and low (db/db-ld) dose groups. The data are shown as mean ± SD.
The blood urea nitrogen (Figure 4) and serum creatinine (Figure 5) levels of the db/m group did not change significantly during the feeding process (P>0.05), while the db/db-m group could be significantly increased during feeding. Week 12 (P <0.01). Treatment with positive drugs and 3 doses of BSR can significantly improve the elevated levels of blood urea nitrogen and serum creatinine in db/db mice (all P <0.01). It is worth noting that compared with the db/db-me group, animals in the db/db-hd group and db/db-md group have lower levels of these two indicators (P <0.01), indicating a significant improvement in high doses And the effect of medium-dose BSR on renal function. Figure 4 The effect of BSR on the blood urea nitrogen level in db/db DN mice (mg/24-hour). The animals were divided into six groups (n = 25): control group (db/m), model group (db/db-m), positive group (db/db-me) and high BSR (db/db-hd), Medium (db/db-md) and low (db/db-ld) dose groups. The data are shown as mean ± SD. Figure 5 The effect of BSR on the serum creatinine level of db/db DN mice (mg/24-hour). The animals were divided into six groups (n = 25): control group (db/m), model group (db/db-m), positive group (db/db-me) and high BSR (db/db-hd), Medium (db/db-md) and low (db/db-ld) dose groups. The data are shown as mean ± SD.
Figure 4 The effect of BSR on the blood urea nitrogen level in db/db DN mice (mg/24-hour). The animals were divided into six groups (n = 25): control group (db/m), model group (db/db-m), positive group (db/db-me) and high BSR (db/db-hd), Medium (db/db-md) and low (db/db-ld) dose groups. The data are shown as mean ± SD.
Figure 5 The effect of BSR on the serum creatinine level of db/db DN mice (mg/24-hour). The animals were divided into six groups (n = 25): control group (db/m), model group (db/db-m), positive group (db/db-me) and high BSR (db/db-hd), Medium (db/db-md) and low (db/db-ld) dose groups. The data are shown as mean ± SD.
H&E staining was used to analyze the histopathological changes in the kidney of db/db mice before and after BSR intervention. The morphology and structure of kidney tissue in the normal control group were normal. Kidney histopathological damage includes glomerular mesangial cell proliferation, mesangial matrix expansion, capillary basement membrane thickening, partial capillary stenosis, vacuolar degeneration of renal tubular epithelial cells, focal renal tubular atrophy and db/db small Interstitial fibrosis in mice can be improved in varying degrees through the intervention of positive drugs and three doses of BSR. Especially in the db/db-hd group of animals, a series of improvements can be observed such as the size of the glomerulus is basically normal, most of the capillary lumen is unobstructed, the renal tubular epithelium is intact, and the interstitial fibrosis is mild (Figure 6). Figure 6 Pathological changes of DN in db/db mice treated with BSR for 24 weeks. The animals were divided into six groups (n = 25): control group (db/m), model group (db/db-m), positive group (db/db-me) and high BSR (db/db-hd), Medium (db/db-md) and low (db/db-ld) dose groups. The data are shown as mean ± SD.
Figure 6 Pathological changes of DN in db/db mice treated with BSR for 24 weeks. The animals were divided into six groups (n = 25): control group (db/m), model group (db/db-m), positive group (db/db-me) and high BSR (db/db-hd), Medium (db/db-md) and low (db/db-ld) dose groups. The data are shown as mean ± SD.
In addition, PAS staining was performed blindly to quantify mesangial expansion, and 20 glomeruli were observed. The degree of mesangial expansion ranges from 0 to 3 points, where 0 means no mesangial expansion and 3 means severe mesangial expansion. The results showed that the kidney tissue of the db/db-md group and the db/db-hd group was significantly better than the db/db-me group in improving the pathological damage of the kidney (Table 1). Table 1 The effect of BSR on the mesangial matrix expansion score of db/db DN mice (after 24 weeks of treatment)
Table 1 The effect of BSR on the mesangial matrix expansion score of db/db DN mice (after 24 weeks of treatment)
In this study, IL-6, TNF-α, TNF-1R and TNF-2R in kidney tissue homogenate were detected by ELISA to further prove the protective effect of BSR on DN. The results showed that the levels of IL-6, TNF-α, TNF-1R, and TNF-2R in the kidney tissue homogenate of the db/m group did not change significantly with the extension of the experimental time (P <0.05). However, the above-mentioned index levels of animals in the db/db-m group were at 8, 12, 16, 20, and 32 weeks (corresponding to 0, 4, 8, 12, and 24 weeks of treatment in the treatment group) (P <0.01). It is worth noting that high (P <0.01), medium (P <0.05) and low (P <0.05) doses of BSR intervention can significantly reduce IL-6, TNF-α, TNF-1R and TNF-2R, and Large doses of BSR have the best effect. In addition, the levels of IL-6, TNF-α, TNF-1R and TNF-2R in the kidney homogenate of the db/db-md group were similar to those of the db/db-me group (P>0.05). These results indicate that medium and high doses of BSR can significantly down-regulate the levels of IL-6, TNF-1R and TNF-2R in kidney tissue (Figure 7, Table 2-5). Table 2 The effect of BSR on the level of IL-6 in db/db mouse kidney tissue homogenate (pg/mL) Table 3 The effect of BSR on the level of TNF-α in db/db mouse kidney tissue homogenate (pg/mL) mL) Table 4 Effect of BSR on the level of TNF-1R in db/db mouse kidney tissue homogenate (pg/mL) Table 5 Effect of BSR on the level of TNF-2R in db/db mouse kidney tissue homogenate (pg/mL) mL) pg/mL) Figure 7 The effect of BSR on the levels of TNF-α, IL-6, TNF-1R and TNF-2R in db/db mouse kidney tissue homogenate (pg/mL). The animals were divided into six groups (n = 25): control group (db/m), model group (db/db-m), positive group (db/db-me) and high BSR (db/db-hd), Medium (db/db-md) and low (db/db-ld) dose groups. The data are shown as mean ± SD.
Table 2 The effect of BSR on IL-6 level in db/db mouse kidney tissue homogenate (pg/mL)
Table 3 The effect of BSR on the level of TNF-α in db/db mouse kidney tissue homogenate (pg/mL)
Table 4 The effect of BSR on the level of TNF-1R in db/db mouse kidney tissue homogenate (pg/mL)
Table 5 The effect of BSR on the level of TNF-2R in db/db mouse kidney tissue homogenate (pg/mL)
Figure 7 The effect of BSR on the levels of TNF-α, IL-6, TNF-1R and TNF-2R in db/db mouse kidney tissue homogenate (pg/mL). The animals were divided into six groups (n = 25): control group (db/m), model group (db/db-m), positive group (db/db-me) and high BSR (db/db-hd), Medium (db/db-md) and low (db/db-ld) dose groups. The data are shown as mean ± SD.
With the clinical application of angiotensin converting enzyme inhibitor (ACEI) and/or angiotensin II receptor blocker (ARB), the treatment of diabetic nephropathy has undergone great changes. However, the clinical application of ACEI and/or ARB failed to reduce the incidence of ESRD in patients with diabetic nephropathy.
Interestingly, traditional Chinese herbal medicines with a long history of use are widely used in the treatment of chronic kidney disease (CKD) in China and other Asian regions. They show good potential in improving clinical symptoms, controlling CKD proteinuria and improving renal function. In addition, in recent years, randomized case-control trials 14-16 have further confirmed the exact effect of Chinese herbal medicine on various kidney diseases, and provided a beneficial strategy for the treatment of various kidney diseases such as DN.
In this study, BSR was obtained by combining Astragalus, Saffron, and Rhubarb in a certain proportion. According to the theory of traditional Chinese medicine, the deficiency of spleen and kidney is the key to the occurrence and development of DN, which determines the development and prognosis of this disease. Blood stasis runs through the entire course of diabetes. It is not only a pathological product of diabetes, but also leads to the occurrence of diabetes. It is also the main cause of various complications such as diabetic DN. The compatibility of the three Chinese herbal medicines has the effects of invigorating the qi and invigorating the spleen, promoting blood circulation and removing blood stasis, dispelling dampness and removing turbidity, and conforms to the pathogenesis of DN. In addition, applying BSR to DN is also in line with the basic principles of TCM syndrome differentiation and treatment of DN.
ACEI and receptor antagonists are commonly used to treat proteinuria. A study reported that in adults, ACEI or ARB can reduce proteinuria by 30-50%. The current guidelines also recommend these for the diagnosis and treatment of DB.17-19. Therefore, in this study, irbesartan was used as a positive control to evaluate the clinical effect of BSR. This study revealed that the blood glucose level of db/db mice began to increase at the 8th week, but the UAER did not increase significantly. Kidney histology showed no significant changes in mesangial cells and matrix. In week 12, UAER rose. In addition, the renal pathology results also showed an increase in mesangial cells and matrix expansion. These indicate the formation of DN. This is consistent with the early changes in DN of db/db mice reported by Simonson20 at 8-16 weeks of age. In this study, low, medium and high doses of BSR were used to treat the db/db mouse model of DN, and the ARB drug irbesartan was used as a positive control. Observe the mice for 24 weeks. The results showed that the body weight, blood glucose, UAER, blood urea nitrogen and creatinine levels of mice in the db/db-ld group, db/db-md group and db/db group were significantly reduced. -HD group. Compared with the db/db-me group, the db/db-hd group and the db/db-md group have obvious advantages in controlling body weight, blood sugar, UAER, blood urea nitrogen, and creatinine levels. The renal pathology results at the same time point also showed that the db/db-md group and the db/db-hd group had significant advantages in reducing the degree of mesangial matrix proliferation and interstitial fibrosis. These results indicate that BSR can improve DN, control proteinuria, improve kidney function, and is superior to ARB drugs in controlling blood sugar and reducing weight.
Modern Chinese medicine studies have shown that Astragalus in the prescription can improve acute kidney injury (AKI) 21 induced by cisplatin and enhance the production of NO induced by LPS in macrophages of patients with renal failure. 22 Astragalus polysaccharide is the active ingredient of Astragalus, which can significantly improve renal failure. Renal pathology and renal fibrosis index of DN caused by streptozotocin 23 The rhubarb in the prescription contains a variety of active ingredients. 24 One of the components emodin can reduce 24-hour proteinuria in diabetic rats, improve kidney pathology, inhibit p38 mitogen-activated protein kinase (MAPK) pathway, reduce the expression of fibronectin in the kidney tissue of DN rats, and improve the kidney Proliferation of glomerular basement membrane. It can prevent the synthesis of extracellular matrix and down-regulate the expression of TNF-α, IL-6 and Toll-like receptor 4 in kidney tissue. 25-27 Rhein, another component, can down-regulate the expression of oxidative stress products, reduce kidney inflammation, reduce TXB2 synthesis, improve renal hemodynamics through anticoagulation, and play a role in renal protection. 24 Rhein can reduce the expression of TNF-α and IL-1β in the kidney tissue of septic rats, inhibit the activity of NF-kB pathway, 28 prevent and treat AKI, and reduce TGF-β in the kidney tissue of obstructive nephropathy and DN rats And α-smooth muscle actin levels. 29,30 Chrysophanol can improve renal interstitial fibrosis-β/Smad signaling pathway by inhibiting TGF and reduce the formation of reactive oxygen free radicals. 31 The saffron in the prescription has anti-inflammatory, antioxidant and insulin sensitizing effects. 32 Milajerdi et al33 conducted a randomized, triple-blind, controlled study of 54 T2DM patients. The results showed that saffron can down-regulate blood sugar and HbA1c. It has been found that saffron extract contains multiple active ingredients. Among them, β-carotene has a variety of biological properties, which can reduce the apoptosis of pancreatic β cells by scavenging free radicals, inhibiting oxidative stress, inhibiting the expression of p53, protecting pancreatic β cells, and improving islet function. Saffron extract can also inhibit the plasma creatinine concentration, malondialdehyde level, TNF-α, ICAM-1 expression and leukocyte infiltration in the ischemia-reperfusion AKI model. 34,35 Based on the above research, the prescription BSR in this study may play a renal protective role in DN by improving islet function, lowering blood sugar levels, inhibiting oxidative stress, improving blood coagulation, and inhibiting inflammation and fibrosis.
Activation of the innate immune system and chronic low-grade inflammation are an important part of the pathogenesis of T2DM. Improving oxidative stress is one of the main treatment goals of DN. Serum IL-6 levels in DN patients are significantly increased, and are significantly related to albuminuria excretion and glomerular basement membrane thickening. 36 TNF-α is a pleiotropic cytokine that can activate a variety of downstream molecules related to vascular endothelial dysfunction, such as ICAM-1, VCAM-1, PAI-1 and systemic inflammation markers, such as IL-6 and C reactive protein. The level of circulating markers in the TNF pathway is closely related to the risk of UER, impaired renal function, and cardiovascular death. 37,38 A cohort study of 410 T2DM patients was observed for 8-12 years. The results showed that 59 patients developed ESRF, and baseline TNF-1R and TNF-2R levels were closely related to the risk of ESRF. 39 In this study, IL-6, TNF-α, TNF1R and TNF2R in kidney tissue homogenate were detected by ELISA in db/db DN model mice to further clarify the anti-inflammatory effect of DN treatment. In this study, the levels of these factors in kidney tissue homogenate were monitored. The results showed that at the age of 12 weeks, the contents of TNF1R, TNF2R, and IL-6 in the kidney tissue of db/db mice in the db/db-m group were significantly increased. After the mice were treated with BSR, the levels of IL-6, TNF1R, and TNF2R in the kidney tissue were significantly reduced, and the corresponding renal tissue pathological results showed that the proliferation of mesangial cells and matrix decreased. These results indicate that BSR may delay the progression of DN by inhibiting inflammation.
Although our data show that BSR can delay the pathological changes in DN mice and reduce the expression of inflammation, the in-depth mechanisms of BSR's potential signaling pathways, targets, and molecular mechanisms on the protection of DN-induced kidney damage still need to be studied in depth. Further Discussion.
In summary, as a traditional Chinese medicine, BSR can effectively delay the pathological damage caused by DN, which is mainly manifested by reducing the levels of a series of indicators such as blood sugar, body weight, urine albumin, blood urea nitrogen, and creatinine, and improving renal function. pathology. In addition, the down-regulation effect of BSR on the levels of renal IL-6, TNF-α, TNF-1R and TNF-2R indicates that BSR may partly play a renal protective effect through anti-inflammatory mechanisms. This study not only demonstrated the protective effect of BSR on DN from the perspective of anti-inflammatory, but also provided a theoretical basis for the development of Chinese herbal medicine therapy for DN.
Follow all applicable international, national and/or institutional guidelines on animal care and use. This study was approved by the Ethics Committee of the Second Hospital of Lanzhou University.
We would like to thank all the staff who implemented the intervention and evaluation part of this research for their hard work and dedication.
Talent Innovation Project of Lanzhou Science and Technology Bureau (2014-RC-64).
The authors declare that they have no competing interests.
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