罗格列酮对肾硬化大鼠模型整合素连接激酶表达的影响  

Influence of rosiglitazone on expression of intergrin-linked kinase in nephrosclerosis rat models

作　　者：崔向飞[1] 韩亚荣[1] 陈硕[1] 陆苗苗[1] 

机构地区：[1]辽宁医学院附属第一医院肾内科,辽宁锦州121001

出　　处：《中国新药与临床杂志》2014年第7期515-519,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：辽宁省教育厅科研基金项目(L2010297)

摘　　要：目的观察罗格列酮对肾硬化大鼠模型整合素连接激酶(ILK)表达的影响。方法 24只大鼠随机分为三组,每组8只。模型组和治疗组行大鼠左肾全切除术,并采用多柔比星诱导局灶节段性肾小球硬化(FSGS)大鼠模型。治疗组于手术当日开始给予罗格列酮3 mg·kg-1·d-1灌胃,每日1次;假手术组和模型组给予等体积生理盐水,均持续12周。采用HE、PAS染色观察肾小球硬化程度,计算肾小球硬化指数;Western blot及免疫组化法检测肾组织中ILK及纤维连接蛋白(FN)蛋白表达情况;RT-PCR检测肾组织中ILK mRNA及FN mRNA的表达水平。结果给药12周后,模型组大鼠肾小球硬化指数、肾小管间质损伤Paller氏评分均较高于假手术组(P<0.05),肾小球明显硬化;治疗组上述指标低于模型组(P<0.05),FSGS减轻。与假手术组相比,模型组大鼠肾组织中ILK及FN的mRNA和蛋白表达水平均明显增加(P<0.05)。治疗组大鼠肾组织中ILK及FN的mRNA和蛋白表达水平均低于模型组(P<0.05)。结论ILK可能参与肾小球硬化的发病,罗格列酮可能通过抑制肾组织ILK的表达来改善肾小球硬化。AIM To observe the influence of rosiglitazone on the expression of intergrin-linked kinase （ILK） in nephrosclerosis rat models. METHODS Twenty-four rats were divided randomly into three groups, each group with 8 rats. Left kidneys of rats in model group and treatment group were given total resection and doxorubicin was used to induce focal segmental glomerulosclerosis （FSGS） rat models. On the day of operation, rats in the treatment group were given intragastric administration with rosiglitazone 3 mg＂ kg-1＂ d-1, once per day; rats in the sham operation group and model group were given normal saline with the same volume. All the treatment lasted for 12 weeks. HE and PAS stain were used to observe the degree of glomerulosclerosis and the glomerulosclerosis index was calculated. Western blot and immunohistochemistry were used to test the expressions of ILK and fibronectin （FN） in nephridial tissues of the rats. The expression level of ILK mRNA and FN mRNA were tested by using RT-PCR. RESULTS After administration, the glomerulosclerosis index and the Paller＇ s score for tubulointerstitial injury of rats in the model group were both higher than those of the sham operation group （P 〈 0.05）, and the glomeruli hardened obviously; the above indexes of treatment group were lower than those of the model group （P 〈 0.05）, and FSGS was alleviated. Compared with the sham operation group, the mRNA and the expression level of ILK and FN in the renal tissues of rats in the model group increased obviously （P 〈 0.05）. The mRNA and expression level of ILK and FN in renal tissues of rats in the treatment group were lower than those of the model group （P 〈 0.05）. CONCLUSION ILK may participate in the development of glomerulosclerosis and rosiglitazone may improve glomerulosclerosis by inhibiting the expression of ILK of nephridial tissues.

关 键 词：罗格列酮 肾硬化症 大鼠 纤连蛋白类 整合素连接激酶 

分 类 号：R965[医药卫生—药理学]