抑制NF-κB对糖尿病大鼠肾组织ICAM-1表达的影响  

Effect of NF-κB Inhibition on ICAM-1 of Diabetic Kidney

作　　者：毛拓华[1] 李竞[1] 刘梦江[1] 秦莹[1] 

机构地区：[1]武汉大学人民医院内分泌科,武汉430060

出　　处：《中国中西医结合肾病杂志》2009年第8期688-691,I0004,共5页Chinese Journal of Integrated Traditional and Western Nephrology

摘　　要：目的:研究糖尿病大鼠肾组织细胞间黏附分子-1(ICAM-1)表达,以及用吡咯烷二硫氨基甲酸(PDTC)抑制核转录因子-κB(NF-κB)对其表达的影响。方法:用Wistar大鼠建立STZ诱导的糖尿病模型,设立正常对照组(NC组)、糖尿病组(DM组)、糖尿病PDTC干预组(DP组),8周末用免疫组化方法测定肾组织中ICAM-1含量;体外培养大鼠肾小管成纤维细胞(NRK),葡萄糖孵育下分6组:正常对照组、高糖1组、高糖2组含葡萄糖分别为5.6、15和30mmol/L,干预1～3组在葡萄糖30mmo/L基础上分别加入PDTC5、10、20μmol/L。24h、48h后采用RT-PCR及免疫细胞化学(ICC)法检测各组的ICAM-1表达情况。结果:8周末,DM组肾组织ICAM-1表达较NC组明显增高,DP组较DM组明显下降,但仍高于NC组。各组NRK细胞中,与正常组相比,高糖各组ICAM-1的mRNA和蛋白表达水平显著升高(P<0.05),且呈剂量时间依赖性;而不同浓度PDTC干预后,ICAM-1mRNA和蛋白表达水平显著下降(P<0.05),而且与PDTC呈剂量时间依赖性。结论:无论在体内或体外实验中,抑制NF-κB可降低ICAM-1的表达。Objective： To investigate the effect of inhibition of NF -kB on ICAM - 1 of diabetic kidney. Methods： 30 healthy male Wistar rats were divided randomly into normal control group（group NC）, diabetic model group（group DM）and diabetic rats with treatment of PDTC （group DP）. Diabetic rats were induced by streptozotocin（STZ）. At the end of 8th week,24 h urine was collected for UAER, and rats kidney were isolated to detect the expression of ICAM - 1 by immunohistochemical staining. NRK cells were cultured in vitro and then divided into control groups with glucose in 5.6 mmol/L,15 mmol/L and 30 mmol/L,respeetively; the experiment groups with PDTC in 5 μmol/L, 10 panol/L and 20 μmol/L on the basis of 30 mmol/L glucose. The expression of ICAM - 1 mRNA was measured by RT - PCR after 24 h and 48 h, respectively. ICAM - 1 was measured by ICC after 24 h and 48 h, respectively. Results： At the end of 8th week, the UAER in the group DM and DP were significantly higher than those in the group NC, and they decreased significantly in the group DP. The expression of ICAM - 1 in the group DM were significantly higher than those in the group NC, and the expression of those in the group DP decreased significantly than those in the group DM, but still higher than those in the group NC. Compared with normal NRK cells groups, the ICAM - 1 mRNA and protein were remarkably increased in a timedose dependent manner exposed to different concentrations glucose （P 〈 0.05） ;the ICAM- 1 mRNA and protein were remarkably decreased in a time - dose dependent manner exposed to different concentrations of PDTC （P 〈 0.05）. Conclusion：Inhibition of NF-kB decreases the expression of ICAM- 1 mRNA and protein in diabetic kidney, and that may play a salutary role in the occurrence and progression of diabetic nephropathy.

关 键 词：糖尿病肾病 细胞间黏附分子-1 核因子-ΚB 吡咯烷二硫氨基甲酸 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]