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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 expression of intercellular adhesion molecule-1 (ICAM-1) in kidney of diabetic rats and its effect on the expression of NF-κB by pyrrolidine dithiocarbamate (PDTC). Methods: The STZ-induced diabetic model was established in Wistar rats. The normal control group (NC group), diabetic group (DM group) and diabetic PDTC intervention group (DP group) were established. At the end of 8th week, the levels of ICAM (NRK) were cultured in vitro. Six rats were divided into 6 groups by glucose: normal control group, high glucose group 1 and high glucose group 2 with glucose of 5.6, 15 and 30 mmol / L, respectively Groups 1 to 3 were given PDTC5, 10 and 20 μmol / L on the basis of glucose 30 mmo / L respectively. The expression of ICAM-1 in each group was detected by RT-PCR and immunocytochemistry (ICC) 24h, 48h later. Results: At the end of the 8th week, the expression of ICAM-1 in DM group was significantly higher than that in NC group. The DP group was significantly lower than DM group, but still higher than NC group. Compared with the normal group, the expression of ICAM-1 mRNA and protein in each group of NRK cells increased significantly (P <0.05), and in a dose-and time-dependent manner; while the intervention of different concentrations of PDTC, ICAM- 1 mRNA and protein expression levels were significantly decreased (P <0.05), and in a dose-and time-dependent manner with PDTC. Conclusion: Inhibition of NF-κB can decrease ICAM-1 expression both in vivo and in vitro.