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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 effect of glycyrrhizin on early glomerulosclerosis in rats. Methods Twice iv adriamycin was used to establish rat glomerulosclerosis model. The experiment was randomly divided into 3 groups, model group, glycyrrhizin treatment group and control group. The indexes of rats in each group were detected at the 4th, 6th and 8th week, including 24 h urinary protein, BUN, SCr, TC and Alb. The renal cortex in each group was examined by light microscopy and histopathology. Immunohistochemistry was used to detect the expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) in renal tissues. The expression of TGF-β1, CTGF and TIMP-1 mRNA in renal tissue were detected by fluorescence quantitative PCR using standard curve method. Results 24-hour urinary protein, BUN, SCr, TC and Alb in the glycyrrhizin treatment group were all improved to some extent (P <0.05) compared with the model group. The degree of glomerulosclerosis in the treatment group was significantly lower than that in the model group. Compared with model group, the expression of TGF-β1 and CTGF protein in the treatment group decreased to some extent and the expression peak decreased (P <0.05). Compared with model group, the expression of TGF-β1, CTGF and TIMP-1 mRNA in the treatment group and the model group decreased to some extent, and the expression peak decreased (P <0.05). Conclusions Glycyrrhizin significantly inhibits the expression of TGF-β1, CTGF and TIMP-1 from the protein and mRNA levels, demonstrating that glycyrrhizin has an early protective effect on glomerulosclerosis in rats.