戊地昔布对高糖培养的肾小管上皮细胞增殖的影响及其调控机制  

Effect of valdecoxib on PI,COX-2 and NF-κB of renal proximal tubular epithelial cells cultured in high glucose medium

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

机构地区：[1]河北医科大学病理学教研室,河北石家庄050017

出　　处：《中国老年学杂志》2009年第13期1666-1668,共3页Chinese Journal of Gerontology

基　　金：河北省科技攻关项目(05276101D-80)

摘　　要：目的探讨戊地昔布对高糖培养的肾小管上皮细胞增殖、核因子(NF)-κΒ、环氧合酶(COX)-2表达的影响。方法将常规培养的人肾小管上皮细胞分为正常糖、高糖和高糖加200μmol/L戊地昔布组,72h后收集细胞,采用流式细胞术检测细胞的增殖指数(PI);免疫细胞化学检测肾小管上皮细胞增殖细胞核抗原(PCNA)和NF-κB蛋白的表达变化,流式细胞术检测肾小管上皮细胞中NF-κB和COX-2蛋白的表达情况。结果(1)与正常糖组比较,高糖组肾小管上皮细胞PCNA表达增强和PI升高(P<0.01或P<0.05);而戊地昔布能够降低高糖培养的肾小管上皮细胞PCNA的表达和PI(P<0.01)。(2)正常糖组,NF-κB主要表达在肾小管上皮细胞的细胞浆内,而高糖组NF-κB表达增强,阳性表达主要定位于肾小管上皮细胞的细胞核内;高糖能够上调肾小管上皮细胞NF-κB活化和COX-2蛋白的表达(P<0.01);高糖加戊地昔布组NF-κB及COX-2表达均降低(P<0.01)。(3)NF-κB和COX-2呈显著正相关;同时COX-2蛋白表达与PI呈显著正相关(P<0.01)。结论降低NF-κB活化、下调COX-2蛋白表达从而降低肾小管上皮细胞增殖可能是戊地昔布保护糖尿病时肾脏损伤的机制之一。Objective To investigate the effect of valdecoxib on the PI, NF-κB/COX-2 signal pathway of human renal proximal tubular cells（HKCs） cultured in high glucose medium. Methods HKCs were cultured separately in normal, high glucose medium or high glucose ＋ 200 μmoL/L for 72 h. The PI was detected by flow cytometry; The expressions of NF-κB and COX-2 protein were detected by flow cytometry and the expression of PCNA was detected by immunocytochemical staining. Results （ 1 ） Compared with those in normal glucose medium group, the expression of PCNA and PI were increased in high glucose medium group, while valdecoxib decreased the expression of PCNA and PI. （2）In normal glucose medium group, NF-κB were positively expressed in cytoplasm, and they were expressed in nucli of HKCs cultured in high glucose medium. The expressions of NF-κB and COX-2 in high glucose medium group were higher than those in normal glucose medium group; which were decreased in high glucose ＋ valdecoxib group. （3）The expressions of NF-κB and PI were positively correlated with the expression of COX-2. Conclusions Valdecoxib has some renal protective effect on diabetic nephropathy, partly through inhibition of cell proliferation by down-regulating NF-κB and decreasing the expression of COX-2.

关 键 词：戊地昔布 高糖 人肾小管近端上皮细胞 核因子-ΚB 环氧合酶-2 

分 类 号：R286.72[医药卫生—中药学]