目的探讨甘草甜素对大鼠肾小球硬化早期的保护作用。方法采用两次经尾iv阿霉素方法建立大鼠肾小球硬化模型。实验随机分为3组,模型组、甘草甜素治疗组和对照组。检测各组大鼠第4、6、8周各项指标的变化,包括24 h尿蛋白定量、血清尿素氮(BUN)、肌酐(SCr)、胆固醇(TC)和白蛋白(Alb)。各组取肾皮质进行光镜等组织病理学检测。应用免疫组织化学方法检测肾组织内转化生长因子β1(TGF-β1)、结缔组织生长因子(CTGF)蛋白的表达。采用标准曲线法进行荧光定量PCR检测肾组织内TGF-β1、CTGF和金属蛋白酶组织抑制物-1(TIMP-1)mRNA的表达。结果甘草甜素治疗组大鼠24 h尿蛋白定量、BUN、SCr、TC和Alb等指标与模型组相比较均有不同程度改善(P<0.05)。肾小球硬化程度治疗组明显轻于模型组。治疗组与模型组比较肾组织内TGF-β1和CTGF蛋白表达均有不同程度降低,表达峰值下降(P<0.05)。治疗组与模型组比较TGF-β1、CTGF和TIMP-1 mRNA表达均有不同程度降低,表达峰值下降(P<0.05)。结论从蛋白和mRNA水平同时证实甘草甜素对TGF-β1、CTGF和TIMP-1的表达有明显的抑制作用,证实甘草甜素对大鼠肾小球硬化有早期保护作用。

Objective To investigate the protective effects of glycyrrhizin(GL) on early glomerulosclerosis.Methods To create glomerulosclerosis models of rat by injecting adriamycin twice in vena caudalis.The rats were randomly divided into following three groups: model group,treatment group,and control group.The level of each index was measured at the week 4,6,and 8.The indexes include: quantitation of 24 h urine protein,serum levels of blood urea nitrogen(BUN),serum creatinine(SCr),cholesterol(TC),albumin(Alb);Histopathologic examination for renal cortex of each group,including light microscope was carried out;Detection of the expression for transforming growth factor-β1(TGF-β1),connective tissue growth factor(CTGF) in the renal cortex by the immunohistochemical method;Detection of the expressione of mRNA of TGF-β1,CTGF,and tissue inhibitor of metalloproteinase-1(TIMP-1) by standard curve with fluorescent quantitation PCR were conducted.Results Treatment group showed an improvement in quantitation of 24 h urine protein,BUN,SCr,Alb,and TC compared with the model group(P0.05).The changes of pathology of kidney in the treatment group were obviously superior to those in the model group.The expression of TGF-β1 and CTGF in the treatment group was lower than those in the model group and the peak value of expression decreased(P0.05).The mRNA expression of TGF-β1,CTGF,and TIMP-1 in the treatment group was lower than those in model group and the peak value of expression decreased(P0.05).Conclusion Glycyrrhizin has a partial protective effect on experimental glomerulosclerosis in rats.

广东省中医药管理局科研基金项目(1050062);广州市科技攻关计划基金项目资助(2006Z3-E0231);广州市中医药中西医结合基金项目(2005A001)