阿托伐他汀对单侧输尿管梗阻大鼠肾小管间质丝裂原活化蛋白激酶p38活性的影响  

Effect of Atorvastatin on the activity of mitogen-activated protein kinase p38 in renal tubular interstitium of rats with unilateral ureteral obstruction

作　　者：陈明[1] 张超[1,2] 彭红霞 欧三桃[1] 刘斌[1] 

机构地区：[1]泸州医学院,附属医院肾内科,肾功能保护研究室 [2]上海市嘉定区南翔医院内科,上海市201802

出　　处：《中国组织工程研究与临床康复》2007年第4期685-688,I0003,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：四川省教育厅重点资助项目(2000128;2004049)~~

摘　　要：目的:观察单侧输尿管梗阻大鼠肾小管间质丝裂原活化蛋白激酶p38、磷酸化丝裂原活化蛋白激酶p38的表达变化,分析丝裂原活化蛋白激酶p38在肾小管间质纤维化发生中的作用及阿托伐他汀抗肾小管间质纤维化的可能机制。方法:实验于2004-09/2005-03在泸州医学院附属医院传染免疫研究室内完成。清洁级SD大鼠45只,数字表法随机分为假手术组、模型组及阿托伐他汀治疗组(简称阿乐组),每组15只。模型组与阿乐组大鼠均行单侧输尿管梗阻术,假手术组仅游离输尿管但不结扎。阿乐组于术前3d开始阿托伐他汀10mg/(kg·d)(混悬于1mL生理盐水中)灌胃,其余两组予等量生理盐水灌胃。术后第5,10,15天分别处死各组中的5只大鼠,取左肾行苏木精-伊红染色和Masson染色,并用免疫组化方法检测肾小管间质中转化生长因子β1、丝裂原活化蛋白激酶p38、P-丝裂原活化蛋白激酶p38的表达。结果:SD大鼠45只全部进入结果分析。①模型组大鼠肾小管间质细胞增多,肾小管基底膜增厚皱缩,纤维化明显,随时间进展而加重;阿乐组大鼠肾小管间质病变程度较同期模型组明显减轻(P<0.01)。②假手术组大鼠肾小管间质中仅有少量转化生长因子β1、丝裂原活化蛋白激酶p38、P-丝裂原活化蛋白激酶p38表达;术后5,10,15d模型组大鼠梗阻侧肾小管间质中转化生长因子β1、丝裂原活化蛋白激酶p38、P-丝裂原活化蛋白激酶p38表达量为较假手术组明显增加(P<0.01),且随时间进展,表达量不断增加;阿乐组均较同期模型组明显减轻(P<0.01)。③实验大鼠肾小管间质丝裂原活化蛋白激酶p38、P-丝裂原活化蛋白激酶p38表达与转化生长因子β1表达均呈正相关(r=0.436,0.432,P<0.01);P-丝裂原活化蛋白激酶p38表达与丝裂原活化蛋白激酶p38表达呈正相关(r=0.447,P<0.01)。结论:丝裂原活化蛋白激酶p38可能参与单侧输尿管梗阻大鼠肾小管间质ALM： To observe the changes in expressions of mitogen-activated protein kinase （MAPK） p38 and phosphorylation MAPK p38 in renal tubular interstitium of rats with unilateral ureteral occlusion （UUO）, and analyze the effect of atorvastatin on renal tubular interstitial fibrosis of p38MAPK and its possible anti-mechanism on renal tubular interstitial fibrosis. METHODS：The experiment was conducted in the Laboratory of Premunltion, Affiliated Hospital of Luzhou Medical College from September 2004 to March 2005. Forty-five SD rats of clean grade were randomly divided into the sham- operation group, model group and atorvastatin treatment group （treatment group）with 15 rats in each group. Rats in the model group and treatment group Wera treated by UUO, while rats in the sham-operation group were only liberate the ureter without deligation. Rats in the treatment group were given gastric perfusion of atorvastatin （10 mg·kg^-1·d^- 1 suspended in 1 mL of normal saline ） at 3 days before operation, while rats in the other two groups were intragastrically administrated with normal saline at the same dose. Five rats in each group were executed respectively at 5, 10 and 15 days after operation. Histological＇ changes in renal tubular interstitium were observed by HE and Masson staining. Immunohlstochemical method was performed on left renal tubular interstitium to detect the expressions of transforming growth factor-β1 （TGF-β1）, P38MAPK and P-P38MAPK in renal tubular Interstitium. RESULTS.A total of 45 SD rats were all involved in the analysis of results. ①The renal interstitial cells increased in rats of the model group with the basal membrane thickened and shrank as well as obvious fibrosis, which were aggravated with the time prolonging. Pathological diseases in renal tubular interstitium in the treatment group were remarkably ameliorated than those in the model group at synchronization （P 〈 0.01）. ②Little amount of renal tubular interstitium in rats of the sham：operation group transfo

关 键 词：丝裂原激活蛋白激酶类 转化生长因于β 肾小管/病理学 吡咯类/药理学 

分 类 号：R965[医药卫生—药理学]