【作者】 孙云松；

【导师】 于俊生；

【作者基本信息】 山东中医药大学 ， 中医内科学， 2011， 博士

【摘要】 目的：运用厥阴病理论探讨和厥阴法治疗慢性肾衰竭的思路,以及和厥阴法对肾纤维化的干预作用。方法：提出慢性肾衰竭厥阴阴枢不利的病机假说,以和厥阴法为治疗大法,精选药物,合理组方,制成和络泄浊颗粒,进行实验研究；采用5/6肾切除大鼠模型,将60例Wistar大鼠随机分为6组：正常组、模型组、西药福辛普利组、中药低剂量组、中剂量组及高剂量组。检测各组血清尿素氮(BUN)、血清肌酐(Scr),取残肾组织行HE染色,光镜观察肾组织病理变化,免疫组化检测细胞外基质的主要成分纤维蛋白(FN)表达的变化。逆转录聚合酶链反应(RT-PCR)及免疫组化检测转化生长因子β1(TGF-β1)、p-Smad2/3、Smad7基因及蛋白表达的变化。结果：和络泄浊颗粒与福辛普利治疗组BUN、Scr水平明显低于模型组(P<0.05)；中西药治疗组大鼠5/6肾切除后肾组织TGF-β1、p-Smad2/3表达减弱,Smad7表达增强,肾组织FN沉积减少,肾小球硬化改善(P<0.05)。结论：慢性肾衰竭具有厥阴阴枢不利的病机特点,和厥阴法是其重要治法；和络泄浊颗粒可调节TGF-β1/smads信号传导通路,改善肾纤维化时ECM主要成分的沉积,保护残存肾功能,延缓肾纤维化的进展。更多还原

【Abstract】 Objective:To discusse the correlation of pathogenesis of chronic renal failure (CRF) with Jueyin disease, the thinging of treating chronic renal failure by mediating-Jueyin, and study the mechanism of the method of mediating-Jueyin interfering in renal fibrosis.Methods:Put fotward the hypothesis that CRF are resulted from Jueyin helm malfunction. Take mediating-Jueyin as treatment method, composing the formula rationally, choosing the medicine carefully, to make the Reconciliating Collaterals and Dispersing Turbid Granula(RDG). Using 5/6 nephrectomy rats divided into 6 groups, which are normal group, model group, treated by Fuxinpuli group, treated by RDG Low-dose group(group I)、RDG middle-dose group(group II) and RDG High-dose group(group III). Observing the weight change of the rat and their biochemical results:blood urea nitrogen(BUN), serum creatinine(Scr). Take the renal tissue from the operative side. HE staining and immunohistochemical methods were used to detect the changes of Fibronectin (FN). immunohistochemical and RT-PCR methods were used to detect the changes of the gene and protein expression of transforming growth factor-β1/Smad singaling Pathway (TGF-β1/Smads).Result:Compared with the untreated 5/6 nephrectomized group, BUN、Scr of RDG groups and Fuxinpuli group were substantially decreased (P< 0.05). The expression of TGF-β1、p-Smad2/3、FN in 5/6 nephrectomy rats is higher than in normal group. It was less in RDG groups and Fuxipuli group (P< 0.05).The expression of Smad7 in 5/6 nephrectomy rats is less than in normal group. It was higher in RDG groups and Fuxipuli group (P< 0.05). extracellular matrix(ECM) was less in RDG groups and Fuxipuli group. The glomerular sclerosis was less in RDG groups and Fuxipuli group. Conclusion:The Jueyin helm malfunction is the pathological characteristic of CRF, the method of mediating-Jueyin is effective on it. The therapy can adjust transforming growth factor-β1/Smad singaling Pathway (TGF-β1/Smads), remarkably improve the pathological lesion of renal tissue, protect the remaining nephron, retard renal fibrosis.更多还原