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目的:观察羟甲基戊二酰辅酶A还原酶抑制剂氟伐他汀(fluvastatin,Flu)对环孢素A(cyclosporine A,CsA)致大鼠肾毒性的保护作用。方法:选择30只健康、雄性SD大鼠,随机分为3组:①对照组:给予蒸馏水和橄榄油灌胃;②肾毒性组:给予CsA 30 mg/(kg·d);③治疗组:给予CsA 30 mg/(kg·d)和Flu 7 mg/(kg·d)。在灌药后的第14天,每组随机处死5只大鼠,实验的第28天,处死其余的大鼠,观察各组肾脏组织学变化,用免疫组织化学技术检测肾组织中Smad2/3、Smad7蛋白及转化生长因子-β1(transforming growth factor-β1,TGF-β1)的表达情况。各组大鼠在每周抽血检测肾功能和脂类水平。结果:在第1周,Flu治疗组的血肌酐(serum creatinine,SCr)与对照组差异无统计学意义(P=0.564)。肾毒性组从第1周开始SCr增高(P=0.000)。肾毒性组在第14天和第28天肾脏的纤维化评分、Smad2/3蛋白及TGF-β1的表达与对照组比较增加(P=0.000),而Smad7蛋白表达明显下调(P=0.000),Flu在这2个时间点能够不同程度地改善这些指标。3组的胆固醇水平在第0、1、2、3和4周之间的差异无统计学意义(P=0.865、0.997、0.505、0.871及0.540),同时各组的甘油三酯水平在相同时间点比较差异无统计学意义(P=0.894、0.663、0.826、0.635及0.928)。治疗组与肾毒性组在第2周和第4周CsA的谷值浓度比较均无统计学差异(P=0.183和P=0.123)。结论:Flu对环孢素A致大鼠肾毒性有保护作用。
Objective: To observe the protective effect of fluvastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, on nephrotoxicity induced by cyclosporine A (CsA) in rats. Methods: Thirty healthy and male Sprague-Dawley rats were randomly divided into three groups: ① control group: intragastric administration of distilled water and olive oil; ② nephrotoxic group: CsA 30 mg / (kg · d); ③ treatment group: CsA 30 mg / (kg · d) and Flu 7 mg / (kg · d) were given. On the 14th day after irrigation, 5 rats were randomly sacrificed in each group. On the 28th day of the experiment, the remaining rats were sacrificed and the renal histological changes were observed. Immunohistochemistry was used to detect the expression of Smad2 / 3 , Smad7 protein and transforming growth factor-β1 (TGF-β1). Rats in each group were tested for renal function and lipid levels on a weekly basis. Results: In the first week, there was no significant difference in serum creatinine (SCr) between Flu treatment group and control group (P = 0.564). Nephrotoxic group SCr increased from the first week (P = 0.000). The renal fibrosis score, the expression of Smad2 / 3 protein and TGF-β1 in nephrotoxic group increased at the 14th and the 28th day compared with the control group (P = 0.000), while the expression of Smad7 protein decreased significantly (P = 0.000) Flu at these two time points can improve these indicators to varying degrees. There were no significant differences in cholesterol levels between the three groups at weeks 0, 1, 2, 3 and 4 (P = 0.865, 0.997, 0.505, 0.871 and 0.540), with triglyceride levels in all groups at the same time The difference was not statistically significant (P = 0.894,0.663,0.826,0.635 and 0.928). There was no significant difference in the trough concentrations of CsA between treatment group and nephrotoxic group at the second week and the fourth week (P = 0.183 and P = 0.123). Conclusion: Flu has protective effect on cyclosporine A-induced nephrotoxicity in rats.