阿司匹林对糖尿病大鼠肾脏COX-2表达的影响

摘要

Objective To observe the expression of cyclooxygenase-2 and pathological change in the kidney of diabetic rats, and study how aspirin influences on the kidney and its possible mechanisms. Methods 24 Sprague Dawley (SD)rats were randomly divided into 3 groups t Control group (C), Diabetes group (D) : received peritoneal injection of streptozocin (STZ,60mg/kg), Aspirin treatment group(DT) received aspirin (lmg. Kg-1. D-l)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 microscope and electron microscope. Moreover, immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were used to examine the expression of COX-2 in the kidney. Results There was no prominent pathological change in C group. The renal pathological and lesions of rats in D group were obvious. The kidney of D group shows extra cellular matrix increasing and basilar membrane thickening. We can also see inflammatory cell infiltrating in the kidney interstitial under light microscope. The kidney glomerulus basilar membranes are uneven thickening and the structure is obscure, the close together foot processes are mainly coalition or losing under electron microscope. Compare with C group, the expression of COX-2 in renal tissue increased in D group. (P<0. 01) However, aspirin treatment could significantly decrease the expression Of COX-2(P<0. 01) and lessen the pathological lesions in comparison with those in D group. Conclusion Aspirin has a reno-protective effect on diabetic rats, it may be mediated by suppressing the expression of COX-2 and attenuating pathological change.%目的 探讨阿司匹林对糖尿病大鼠肾脏COX-2表达和病理的影响及其可能的作用机制.方法 将24只SD大鼠随机分成3组,分别为正常对照(C)组、糖尿病(D)组[腹腔注射链酶佐菌素(STZ) 60mg/kg]和糖尿病阿司匹林治疗(DT)组(先腹腔注射STZ 60mg/kg,第4天起给予0.9％氯化钠溶液溶解的阿司匹林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COX-2的蛋白表达和COX-2mRNA的表达.结果 C组大鼠肾脏无明显病理变化；D组大鼠肾脏在光镜下可见细胞外基质增多,基底膜增厚,间质区可见炎性细胞浸润；DT组基质轻度增生,有少量炎性细胞浸润.在电镜下D组显示肾小球细胞基底膜不均匀,结构模糊,相邻足突大部分融合或缺失；DT组病理改变较D组减轻.D组大鼠COX-2蛋白表达较C组显著上调;DT组较D组显著下调.D组大鼠COX-2mRNA在肾脏的表达较C组显著上调(P＜0.01),DT组较D组显著下调(P＜0.01).结论 阿司匹林可以改善糖尿病大鼠肾脏的病理改变,其机制可能是通过抑制COX-2表达,改善由COX-2介导的病理改变.