五苓散与麻黄五苓散对阿霉素肾病大鼠肾功能保护效应的比较研究

Comparative Research on the Protective Effect of Wuling San and Mahuang Wuling San on Renal Function in Rats with Adriamycin Induced Nephropathy

目的观察并比较五苓散与麻黄五苓散对阿霉素肾病(adriamycin nephropathy,AN)模型大鼠的干预效应,并研究其作用机制。方法50只SD大鼠随机分成5组,即空白对照组、模型组、贝那普利组、五苓散组、麻黄五苓散组。除空白对照组外,所有大鼠采用尾静脉注射盐酸阿霉素方法复制大鼠肾病模型。各给药组分别灌胃相应药物,给药期间监测大鼠每周体质量;5周后检测24 h尿量和尿蛋白;检测血清中肌酐(serum creatinine,SCr)、血尿酸(serum uric acid,SUA)、尿素氮(blood urea nitrogen,BUN)含量;Western blot检测肾组织中肾病蛋白(nephrin)、足突蛋白(podocin)表达水平;HE染色观察大鼠肾组织病理变化。结果与空白对照组比较,模型组大鼠平均体质量显著下降(P<0.01),尿量减少(P<0.05),24 h尿蛋白显著增加(P<0.01),SCr、SUA及BUN水平均显著升高(P<0.01),HE染色显示肾组织细胞形态不规则,胞核变形,染色质边集,nephrin、podocin蛋白表达显著下降(P<0.01)。与模型组比较,麻黄五苓散组大鼠平均体质量增加(P<0.01),尿量增加(P<0.05),24 h尿蛋白含量明显降低(P<0.05),SUA和BUN水平显著下降(P<0.01),大鼠肾组织微观病理损伤明显减轻,nephrin、podocin蛋白表达显著升高(P<0.01)。与五苓散组比较,麻黄五苓散组大鼠尿量显著增加(P<0.01),24 h尿蛋白含量明显减少(P<0.05),nephrin蛋白表达显著升高(P<0.01)。结论麻黄五苓散可有效抑制阿霉素肾病大鼠肾组织损伤,降低尿蛋白,改善肾功能。与五苓散比较,麻黄五苓散具有更明显的利尿和抑制尿蛋白作用。

Objective To observe and compare the intervention effects of Wuling San and Mahuang Wuling San on adriamycin nephropathy(AN)rats and study their mechanisms of action.Methods Fifty SD rats were randomly divided into five groups:control group,model group,benazepril group,Wuling San group,and Mahuang Wuling San group.Except for the control group,the rat model of nephropathy was established by tail vein injection of adriamycin hydrochloride.Each treatment group was intragastrically administered with the corresponding drugs,the body weight of rats was monitored weekly,and 24-hour urine volume and urine protein were measured after five weeks,SCr,SUA,and BUN levels were measured,the expression levels of nephrin and podocin were detected by Western blot,and pathological changes in renal tissues were observed by HE staining.Results Compared with the control group,the model group showed a significant decrease in body weight(P<0.01),reduced urine volume(P<0.05),significantly increased 24-hour urine protein(P<0.01),and significantly increased levels of SCr,SUA,and BUN(P<0.01).HE staining showed irregular cell morphology,deformed nuclei,chromatin marginalization,and significantly suppressed expression levels of nephrin and podocin proteins(P<0.01).Compared with the model group,the body weight and urine volume increased(P<0.05),the 24-hour urinary protein decreased significantly(P<0.05),the SUA and BUN levels decreased significantly(P<0.01),the microscopic pathological damage of rat kidney tissue was significantly alleviated,and the expression of nephrin and podocin increased significantly in the Mahuang Wuling San group(P<0.01).Compared with the Wuling San group,the Mahuang Wuling San group showed a significant increase in urine volume(P<0.01),a significant decrease in 24-hour urine protein(P<0.05),and a significant increase in nephrin protein expression(P<0.01).Conclusion Mahuang Wuling San can effectively inhibit renal tissue injury,reduce urinary protein,improve renal function in rats with AN.Compared with Wuling San,Mahuang Wuling San has more pronounced diuretic and proteinuria-inhibiting effects.