当归补血汤对糖尿病肾病大鼠肾纤维化的影响及可能机制。

Zhao Ye, Wang Xian, G U Ling, L I Zihang, Zhu Jingtian, Wang Wenkai, Zhang Liang, Xue Mei
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摘要

目的:观察当归补血汤对糖尿病肾病大鼠肾纤维化的影响,并探讨其可能的作用机制。方法:将60只雄性Goto Kakizaki (GK)大鼠随机分为模型组、格列酮组、黄芪甲苷组和DBD高、中、低剂量组。8周后,观察大鼠体重、血糖、血清肌酐、血清尿素氮、总胆固醇的变化。观察转化生长因子-β1 (TGF-β1)、Smad3、Smad5通路及纤维化相关蛋白胶原IV (col IV)、α-平滑肌肌动蛋白(α-SMA)、vimentin的表达变化。采用免疫组化、Mason染色观察肾纤维化程度。采用酶联免疫吸附法检测肾组织中白细胞介素6 (IL-6)、白细胞介素10 (IL-10)、肿瘤坏死因子(TNF-α)、c反应蛋白(CRP)的表达。结果:我们的实验显示,DBD在给药8周后能有效降低血糖、血尿素氮、肌酐水平,改善糖尿病大鼠肾功能,减轻肾纤维化,降低肾组织中IL-6、IL-10、TNF-α、CRP水平。DBD降低肾组织中TGF-β1、Smad3、col IV、α-SMA、vimentin的表达,增加Smad5的表达。结论:DBD通过调节TGF-β1/Smads通路改善糖尿病肾间质纤维化。
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Efficacy of Danggui Buxue decoction on diabetic nephropathy-induced renal fibrosis in rats and possible mechanism.
OBJECTIVE To observe the efficacy of Danggui Buxue decoction (, DBD) on diabetic nephropathy-induced renal fibrosis in rats, and to study the possible mechanism. METHODS Sixty male Goto Kakizaki (GK) rats were randomly assigned to the model group, gliquidone group, astragaloside IV group, and high-, medium- and low-doses DBD groups. After 8 weeks, changes in body weight, blood glucose, serum creatinine, serum urea nitrogen, and total cholesterol were observed. Changes in transforming growth factor-β1 (TGF-β1), Smad3, and Smad5 pathways and the expression of the fibrosis-related proteins collagen IV (col IV), α-smooth muscle actin (α-SMA), and vimentin were assessed. The degree of renal fibrosis was observed by immunohistochemistry and Mason staining. The expression of interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor (TNF-α), and C-reactive protein (CRP) in the kidneys was assessed using enzyme linked immunosorbent assay. RESULTS Our experiments showed that DBD effectively reduced blood glucose, blood urea nitrogen, and creatinine levels after 8 weeks of administration, improved renal function in diabetic rats, alleviated renal fibrosis, and reduced the renal tissue levels of IL-6, IL-10, TNF-α, and CRP. Furthermore, DBD decreased the expression of TGF-β1, Smad3, col IV, α-SMA, and vimentin in renal tissues and increased the expression of Smad5. CONCLUSIONS DBD ameliorates diabetic renal interstitial fibrosis by modulating the TGF-β1/Smads pathway.
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