核转录因子κΒ/环氧化酶-2参与糖尿病肾病大鼠肾细胞增殖  

Proliferation of renal cells involved by NF-κB/COX-2 signal pathway in diabetic nephropthy

作　　者：刘淑霞[1] 张玉军[1] 张景坤[1] 刘青娟[1] 唐丽娟[1] 段惠军[1] 

机构地区：[1]河北医科大学病理教研室,河北石家庄050017

出　　处：《基础医学与临床》2008年第9期944-948,共5页Basic and Clinical Medicine

基　　金：河北省科技攻关项目(05276101D-80)

摘　　要：目的探讨核转录因子-κΒ(NF-κΒ)/环氧化酶-2(COX-2)信号与糖尿病肾病大鼠肾细胞增殖的关系。方法单侧肾切除大鼠ip链脲佐菌素诱发糖尿病模型,16周后切除左肾。用免疫组织化学检测肾皮质NF-кB和COX-2蛋白的表达;用正常糖和高糖培养基培养肾小管上皮细胞,24、48和72h后收集细胞,用免疫细胞化学检测PCNA蛋白的表达,流式细胞术检测NF-кB和COX-2蛋白的表达。结果(1)糖尿病模型组肾脏肥大指数增加,肾小球体积增大,系膜基质增多;(2)糖尿病模型组肾组织中活化的NF-кB和COX-2蛋白表达高于对照组,两者呈显著正相关;(3)高糖组肾小管上皮细胞PCNA表达强于正常糖组;(4)高糖能够上调肾小管上皮细胞NF-кB和COX-2蛋白的表达,两者呈显著正相关;同时COX-2蛋白表达与PCNA阳性率呈显著正相关。结论活化NF-κB,上调COX-2蛋白表达从而引起肾脏固有细胞的增殖可能是糖尿病肾脏损伤的机制之一。Objective To investigate the correlation between NF-KB/COX-2 signal pathway and cell proliferation in diabetic nephropathy. Methods Uninephrectomized STZ-induced male Wister rats were used as animal model. Using immunohistochemistry to detect NF-KB and COX-2 protein expressions in diabetic kidneys at the 16th week. HKC were cultured separately in normal or high glucose medium for 24,48,72 h. The expression of NF-KB and COX-2 protein was detected by flow cytometry and the expression of PCNA was detected by immunocytochemical staining. Results 1 Volum of glomeruli, mesangial matrix, thickness of glomerular and tubular basement membrane increased in diabete group; 2 COX-2 were expressed in cytoplasm of tubules and glomeruli by immunohistochemistry. Compared with control group, the expression of COX-2 was higher; activated NF-KB expressed in nucli of both tubules and glomeruli, There was light stainings for in control group, while enhanced stainings were observed in DM, there was a positive correlation between NF-KB and COX-2. 3 Compared with those in HKC cultured in the medium with normal level glucose, the stainings were strengthened for PCNA in HKC exposed to high glucose from 24 h. 4 By FCM, the expression of NF-KB and COX-2 in HKC cultured in high glucose medium was higher than that in normal glucose medium; the expression of NF-KB and PCNA was positively correlated with the expression of COX-2. Conclusion Activating NF-KB and elevating the expression of COX-2 play an important role in regulating cell proliferation, which may be one of the injury mechanisms of the renal cells during diabetic nephropathy.

关 键 词：糖尿病肾病 细胞增殖 核因子-KB 环氧化酶-2 

分 类 号：R692[医药卫生—泌尿科学]