阿托伐他汀钙片对肾病综合征模型大鼠肾损伤的改善作用及机制研究

目的:研究阿托伐他汀钙片对肾病综合征模型大鼠肾损伤的改善作用,并探讨其可能的作用机制。方法:取Wistar大鼠随机分为正常组、模型组和阿托伐他汀钙片组,每组10只,模型组和阿托伐他汀钙片组大鼠尾静脉注射剂量为6 mg/kg的阿霉素,连续给药21 d复制肾病综合征模型,从第22天起阿托伐他汀钙片组大鼠灌胃剂量为8 mg/kg的药物,同时正常组和模型组大鼠灌胃等量蒸馏水,每天给药1次,每周连续给药6 d,连续给药10周。末次给药第2天,检测各组大鼠血浆白蛋白(ALB)、总蛋白(TP)、胆固醇(CH)、尿蛋白排泄率(UAE)水平;采用实时定量聚合酶链式反应(RT-PCR)法和Western blot法检测肝组织中腺苷酸活化蛋白激酶(AMPK)、沉默信息调节因子1(SIRT1)、核转录因子κB(NF-κB)mRNA及其蛋白的表达水平。结果:与正常组比较,模型组大鼠ALB、TP水平以及AMPK、SIRT1 mRNA和蛋白表达水平均明显降低(P<0.01或P<0.001),CH、UAE水平以及NF-κB mRNA和蛋白表达水平均明显增加(P<0.05或P<0.01或P<0.001)。与模型组比较,阿托伐他汀钙片组大鼠ALB、TP水平以及AMPK、SIRT1 m RNA和蛋白表达水平均明显增加(P<0.05或P<0.01或P<0.001),CH、UAE水平以及NF-κB mRNA和蛋白表达水平均明显降低(P<0.05或P<0.01或P<0.001)。结论:阿托伐他汀钙片具有明显改善肾病综合征模型大鼠肾损伤的作用,其作用机制可能与上调AMPK、SIRT1表达和下调NF-κB表达有关。

Study on Improvement Effects of Atorvastatin Calcium Tablets on Renal Injury in Nephrotic Syndrome Model Rats and Its Mechanisms

OBJECTIVE:To study the improvement effects of Atorvastatin calcium tablets on renal injury in nephrotic syndrome model rats,and to explore its possible mechanism.METHODS:Wistar rats were randomly divided into normal group,model group and Atorvastatin calcium tablets group,with 10 rats in each group.Model group and Atorvastatin calcium tablets group rats were given adriamycin 6 mg/kg intravenously for consecutive 21 d to induce nephrotic syndrome model.Since 22th day,Atorvastatin calcium tablets group was given drug 8 mg/kg intragastrically while normal group and model group rats were given equal amount of distilled water intragastrically,once a day,consecutive 6 days every week,for consecutive 10 weeks.At the second day after last medication,the plasma levels of albumin(ALB),total protein(TP),cholesterol(CH),urine albumin excretion rate(UAE)were determined in each group.RP-PCR and Western blot assay were used to detect mRNA and protein expression of AMP-activated protein kinase(AMPK),silent information regulator 1(SIRT1)and nuclear factorκB(NF-κB)in liver tissue.RESULTS:Compared with normal group,the levels of ALB and TP,mRNA and protein expression of AMPK and SIRT1 were decreased significantly in model group(P<0.01 or P<0.001),while the levels of CH and UAE,mRNA and protein expression of NF-κB were increased significantly(P<0.05 or P<0.01 or P<0.001).Compared with model group,the levels of ALB and TP,mRNA and protein expression of AMPK and SIRT1 were increased significantly in Atorvastatin calcium tablets group(P<0.05 or P<0.01 or P<0.001),while the levels of CH and UAE,mRNA and protein expression of NF-κB were decreased significantly(P<0.05 or P<0.01 or P<0.001).CONCLUSIONS:Atorvastatin calcium tablets has significant improvement effect on the renal injury of nephritic syndrome model rats,the mechanism of which may be associated with up-regulating the expression of AMPK and SIRT1 and down-regulating the expression of NF-κB.