罗格列酮对糖尿病大鼠肾脏病理改变的影响

Influence of rosiglitazone on the pathological change of the kidney of diabetic rats.

目的观察罗格列酮对糖尿病大鼠肾脏组织病理改变的影响并探讨其作用机制。方法24只SD大鼠随机分成3组，糖尿病组：腹腔注射含链酶佐菌素（STZ）60mg／kg；罗格列酮治疗组：先腹腔注射STZ60mg／kg，第4天起给予0．9％氯化钠溶液溶解的罗格列酮1mg／（kg·d）灌胃。8周后，观察3组肾脏组织在光镜、电镜下的病理表现，用免疫组化法和逆转录．聚合酶链式反应法观察环氧化酶-2（COX-2）的蛋白表达和COX-2mRNA的表达。结果正常对照组大鼠肾脏无明显病理变化。糖尿病组大鼠肾脏在光镜下显示肾小球细胞外基质增多，基底膜增厚，肾小管有炎症细胞浸润；在电镜下显示肾小球细胞基底膜不均匀，相邻足突大部分融合或缺失。罗格列酮治疗组病理改变较糖尿病组减轻。糖尿病组大鼠COX-2蛋白表达较正常对照组明显上调，罗格列酮组较糖尿病组明显下调。糖尿病组大鼠COX-2mRNA（0．474±0．012）在肾脏的表达较正常对照组（0．342±0．016）显著上调（P〈0．01），罗格列酮组（0．369±0．025）较糖尿病组显著下调（P〈0．01）。结论STZ诱导的糖尿病大鼠的肾脏具有COX-2介导的病理改变，罗格列酮可以抑制COX-2的表达，改善糖尿病大鼠肾脏的病理改变。

Objective To investigate the influence of rosiglitazone on renal pathological change of diabetic rats induced by STZ and its possible mechanisms. Methods Twenty four Sprague Dawley （SD）rats were randomly divided into 3 groups ： Control group （ C）, Diabetes group （D） ： received peritoneal injection of streptozocin （ STZ, 60 mg/kg） , Rosiglitazone treatment group（DR） ：received rosiglitazone[ 1 mg/（ kg·d） ] from the fourth day after treatment as in group D. At the end of 8 weeks, the pathological changes in the kidney were observed under light mi- croscope and electron microscope. Moreover, immunohistochemistry and reverse transcription polymerase chain reaction （RT-PCR） were used to examine the expression ofcyclooxygenase-2（COX-2） in the kidney. Results There is no prominent pathological change in C group. The renal pathological and lesions of rats in D group were obvious. The kidney of D group showed extra cellular matrix increasing and basilar membrane thickening. Inflammatory cell infil- trated in the kidney tubules under light microscope. The kidney zlomendus basilar membranes were thickening uneverily, the close together foot processes were mainly coalition or losing under electron microscope. Compared with C group（0. 342±0. 016）, the expression of COX-2 in renal tissue increased in D group（ 0. 474 ± 0. 012） （P 〈 0.01 ）. However, rosiglitazone treatment could significantly decrease the expression of COX-2 （0. 369 ± 0.025） （ P 〈 0.01 ） and lessen the pathological lesions in comparison with those in D group. Conclusions Rosiglitaznne has a reno-protective effect on diabetic rats induced by STZ, it may be mediated by suppressing the expression of COX-2 and attenuating pathological change.