阿托伐他汀抑制Rac1减轻嘌呤毒素氨基核苷诱导的大鼠肾病综合征  

Atorvastatin Ameliorates Puromycin Aminonucleoside Induced Ne- phropathyby Inhibiting Racl Signaling in Rats

作　　者：刘柳[1] 高红宇[1] 何晓峰[1] 王芳[1] 潘昊[1] 徐钢[1] 吕永曼[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院肾内科,武汉市430030

出　　处：《医学分子生物学杂志》2015年第5期249-253,共5页Journal of Medical Molecular Biology

基　　金：国家自然科学基金（No.81200521,81100481）

摘　　要：目的他汀类药物被发现具有减轻肾病大鼠蛋白尿的作用，本研究试图证明阿托伐他汀是否通过抑制Rac1减轻。肾病综合征。方法通过给sD大鼠一次性腹腔注射嘌呤毒素氨基核苷（puromycinamino．nucleoside．PAN）的方法制备大鼠肾病综合征模型，设对照组、模型组和阿托伐他汀治疗组。免疫荧光法检测大鼠肾小球中nephrin和podocin的表达，Western印迹检测Racl的表达。结果与正常对照组相比，模型组大鼠表现为典型的肾病综合征：尿蛋白排泄量明显增加[（199．23±68．04）mg／24h]，血白蛋白明显降低[（15．28±1．93）g／L]，血胆固醇明显升高[（8．54±2．01）mmol／L]；阿托伐他汀治疗后显著地降低了尿蛋白[（128．49±75．61）mg／24h]和血胆固醇[（4．23±1．44）mmol／L]而提高了血白蛋白水平[（22．45±4．24）g／L]。与正常对照组相比，模型组大鼠肾小球中nephrin和podocin表达降低，细胞膜的Rac1表达上调，他汀治疗后能上调nephrin和podocin表达以及抑制Rac1在细胞膜的表达。结论阿托伐他汀能够减轻PAN大鼠蛋白尿，减轻PAN所导致的足细胞损伤，这一效应可能是通过抑制Rac1活化来实现的。Objective Statins have been reported to reduce the amount of urinary nephrotic syndrome rats. The objective of this study was to explore whether atorvastatin protein in ameliorates puromycin aminonucleoside （PAN） induced nephropathy via inhibiting Racl signaling. Methods Rat nephrotic syndrome model was induced by iutraperitoneal injection of single dose of PAN. Animals were divided into three groups： control group, model group, and atorvastatin group. The expressions of podocin and nephrin were determined by immunofluorescence, and the ex- pression of Racl was detected by Western blotting. Results Compared with the control group, u- rine protein excretion was extremely increased [ （199. 23 ±68.04） mg/24h], serum albumin levels decreased [ （ 15.28 ± 1.93 ） g/L] and cholesterol level increased [ （8.54 ± 2. 01 ） mmol/L] in model group. Atorvastatin treatment obviously decreased the levels of urine protein [ （128.49 ± 75.61 ） mg/24h] and cholesterol [ （4. 23 ± 1.44） mmol/L], and increased serum albumin level [ （22. 45 ±4. 24 ） g/L] . Reduction of nephrin and podocin in glomerulus and increase of mem-brahe Racl expression were detected in model group compared with control group. After treatment of atorvastatin, the expressions of nephrin and podocin were raised, and the expression of Racl on the membrane was inhibited. Conlusion Atorvastatin can decrease urine protein excretion, and allevi- ate podocyte injury by inhibiting Racl signaling in rats with PAN-induced nephropathy.

关 键 词：阿托伐他汀 嘌呤毒素氨基核苷 足细胞 RAC1 

分 类 号：R349.7[医药卫生—基础医学]