阿托伐他汀对单侧输尿管梗阻大鼠肾小管间质过氧化物酶体增殖物激活受体γ表达的影响  

Effects of atorvastatin on expression of peroxisome proliferation activated receptor γ in unilateral ureteral obstruction in rats

作　　者：刘斌[1] 陈明[1] 彭红霞[1] 张超[1] 欧三桃[1] 

机构地区：[1]四川省泸州医学院附属医院肾内科、泸州医学院肾功能保护研究室,646000

出　　处：《中国危重病急救医学》2007年第12期739-741,I0002,共4页Chinese Critical Care Medicine

基　　金：四川省教育厅重点课题资助项目（2004A068）

摘　　要：目的观察阿托伐他汀对单侧输尿管梗阻（UUO）大鼠肾小管间质过氧化物酶体增殖物激活受体γ（PPARγ）表达的影响。方法将45只大鼠随机均分为假手术组、模型组及阿托伐他汀组（阿乐组），后两组行左侧输尿管结扎术。阿乐组术前3d开始给予阿托伐他汀（10mg·kg^-1·d^-1）灌胃，其余两组予等量生理盐水灌胃。术后5、10和15d分别处死各组5只大鼠，取左肾行苏木素-伊红（HE）和Masson染色，动态观察肾脏病理改变，并用免疫组化方法检测肾小管间质中PPARγ的动态表达。结果组织病理学显示，模型组呈现进行性肾小管间质面积增宽，纤微化程度加重。假手术组PPARγ主要表达于内髓集合管；模型组PPARγ表达则位于肾小管上皮细胞，半定量分析显示UUO后5d PPARγ已经明显增高，梗阻后10d达到峰值，15d PPARγ已降低，但仍高于假手术组（P均〈0．01）。阿乐组肾小管间质中PPARγ表达较同期模型组明显增加（P均〈0．01）。结论UUO模型大鼠肾小管间质PPARγ的表达量增加，并在肾小管部位出现PPARγ的表达；阿托伐他汀可增加PPARγ的表达，从而改善肾小管间质纤维化。Objective To observe the expression of peroxisome proliferation activated receptor γ （PPARγ） at different periods in renal interstitium and to study the effect of atorvastatin on the protein expression of PPARγ in unilateral ureteral obstruction （UUO） in a rat model. Methods Forty-five female Sprague -Dawley （SD） rats were divided into three groups, the sham operation group, the model group and the atorvastatin group. The latter two groups underwent UUO and then received vehicle only or atorvastatin （10 mg · kg^-1 · d^-1） by daily gastric gavage, from three days before the UUO operation to the day of sacrifice. The sham operation rats received vehicle. Five rats of each group were sacrificed respectively at 5, 10 and 15 days after surgery. Histological changes in renal tissue were observed by hematoxylin and eosin （HE） and Masson stain, Immunohistochemistry for PPARγ was performed in renal interstitum at each time point. Results Interstitial expansion and fibrosis in ureter obstructed kidney was prominent in the model group. Atorvastatin seemed to have ameliorated interstitial expansion and fibrosis in atorvastatin group. Detectable basic PPARγ expression was observed in renal inner medulla of rats in sham operation group, and it was mainly concentrated in collecting tubules. In UUO rats, PPARγ expression was found increased and extended to renal tubular epithelial cells. Increased PPARγ expression was found on the 5 th day after UUO, and significant PPARγ expression was found on the 10 th day after UUO. The increased PPARγ expression was found to be downregulated on the 15 th day after UUO, but still significantly increased compared with that of the model group at the same time point （all P〈0.01）. Atorvastatin could significantly increase the expression of PPARγ as compared with the model group at each time point （all P〈0.01）. Conclusion PPARγ expression was found increased, and it appeared in renal tubular epithelial cells in UUO rats, Atorvastatin may play a protect

关 键 词：纤维化 肾间质 过氧化物酶体增殖物激活受体Γ 阿托伐他汀 

分 类 号：R686[医药卫生—骨科学]