真武汤对阿霉素所致大鼠肾损伤的治疗作用

Effects of Zhenwu decoction on rat kidney injury induced by adriamycin

目的:研究真武汤对阿霉素肾病模型(adriamycin nephropathy,AN)大鼠足细胞裂孔隔膜蛋白分子(podocin和nephrin)表达的影响,探讨其防治阿霉素肾病大鼠蛋白尿的机制。方法:采用常规生化、病理方法(包括HE染色、Masson染色及电镜)观察真武汤对AN模型所致纤维化大鼠肾功能、肾组织形态学变化及羟脯氨酸(Hyp)含量的改善作用;采用蛋白免疫印迹等方法探索真武汤对足细胞标志蛋白podocin和nephrin信号分子表达的影响。结果:模型组大鼠尿蛋白(TP)、血尿素氮(BUN)和血清肌酐(SCr)显著增加,肌酐清除率(CCr)显著下降(P<0.05);Hyp显著增加(P<0.05);肾组织podocin和nephrin蛋白表达水平显著降低(P<0.05);肾小管萎缩,基底膜增厚;足突扁平、融合、消失。肾小球集中现象明显;部分肾小管扩张,肾小管上皮细胞变性,蛋白管型明显;肾间质纤维组织增生和较多炎症细胞浸润。与模型组相比,各治疗组TP、BUN和SCr均有一定程度的下降,CCr显著提高;Hyp明显下降(P<0.05);真武汤组肾组织podocin和nephrin蛋白表达水平显著提高(P<0.05);肾组织病变程度轻于模型组。结论:真武汤能减少阿霉素肾病大鼠肾组织羟脯氨酸含量,改善肾功能及减轻病理损伤。真武汤降低模型大鼠蛋白尿的作用可能与其维持足细胞podocin和nephrin的表达有关。

AIM： To observe the effects of Zhenwu decoction on the expression of podocin and nephrin in podocytes of adriamycin nephropathy （AN） rats, and to clarify the mechanism of Zhenwu decoction in decreasing adriamycin-induced proteinuria in rats. METHODS： Biochemical assay and pathological observation （HE staining, Masson trichrome staining and transmission electron microscopy） were used to evaluate the effects of Zhenwu decoction on renal function, pathological morphology and hydroxyproline （Hyp） content in AN rats with renal fibrosis. Western blotting was used to observe the effect of Zhenwu decoction on the expression of podocin and nephrin which are marker proteins in podocytes. RESULTS： In model group, the levels of urinary total protein （TP）, blood urea nitrogen （BUN）, serum creatinine （SCr） and renal Hyp were significantly increased, and the clearance of creatinine （CCr） level was decreased （ P 〈 0.05 ）. The expression of podocin and nephrin was significantly decreased （ P 〈0. 05）. Atrophic renal tubules, thickened basement membranes, fusion of foot processes, concentrating renal glomerules, expansion of some renal tubules, degeneration of renal tubular epithelial cells, protein casts, and proliferation of fibroblasts and infiltration of inflammatory cells in renal interstitium were also observed. After treatment with drugs （ Zhenwu decoction and valsartan）, the above-mentioned parameters were significantly changed. TP, BUN, SCr and Hyp were down-regulated to different levels, and CCr was significantly up-regulated （P 〈 0.05 ）. The expression of podocin and nephrin was up-regulated by treatment with Zhenwu decoction, and renal histological changes were alleviated compared with model group. CONCLUSION： Zhenwu decoction can reduce Hyp content in kidney tissue, alleviate kidney histological changes, and improve renal function in AN rats. It might protect kidney against adriamycin-induced proteinuria via increasing the expression of podocin and nephrin in podocytes.