罗格列酮对高糖诱导的系膜细胞核因子-κB活性及细胞间黏附分子1表达的影响

Inhibitory effects of rosiglitazone on activation of NF-κB and expression of ICAM-1 induced by high glucose in rat mesangial cells

目的探讨罗格列酮对高糖诱导的大鼠系膜细胞表达细胞间黏附分子1(ICAM-1)的影响及其可能机制。方法采用正常糖(NG)、高糖(HG)及HG+不同浓度罗格列酮培养大鼠系膜细胞。以RT-PCR检测ICAM-1 mRNA的表达,采用ELISA检测培养细胞上清中ICAM-1蛋白的浓度。采用凝胶电泳迁移率改变法检测NF-κB的活性。结果HG组ICAM-1/GAPDH吸光度是NG组的2.9倍(P<0.01)。5μmol/L及20μmol/L罗格列酮均可显著抑制ICAM-1 mRNA的表达。HG刺激系膜细胞1 h可使NF-κB活性增强2.5倍(P<0.01),高糖诱导的NF-κB的活化可被罗格列酮(20μmol/L)所抑制(0.8±0.2vs2.5±0.3,P<0.01)。结论罗格列酮可通过抑制NF-κB信号传导途径降低高糖诱导的系膜细胞ICAM-1的表达。

Objective To investigate the role of rosiglitazone in high glueose（HG） induced intercellular adhesion moleeule-1（ICAM-1） expression of rat mesangial cells. Methods The rat mesangial cells （MCs） were cultured in the medium with normal glucose （5.6 retool/L, NG）, high glucose （25 retool/L, HG）, HG＋ 5 /lmol/L rosiglitazone, HG＋ 20 /lmol/L rosiglitazone and HG＋ PDTC （αNF-κB inhibitor）. ICAM-1 mRNA expression was measured by semi-quantitative RT-PCR assay. Activation of nuclear factor-κB（NF-κB） of rat mesangial cells was measured by eleetrophoretie mobility shift assay （EMSA）. The levels of ICAM-1 in the supernatants were determined by enzymelinked immunosorbant assay （ELISA.） Results RT PCR results showed that high-glucose increased the ratio of PCR products of ICAM-1 over GAPDH to 2.9-fold, which was prevented by rosiglitazone （5 and 20 μmol/L） pre-treatment. The NF-κB binding activity was 2.5-fold higher in MCs exposed to HG as compared with NG （P〈0.01）. When the MCs were cultured in the presence of rosiglitazone （20μmol/L） for 1 h,there was a highly significant reduction in NF-κB binding activity （0.8±0.2 vs 2.5±0.3, P〈0.01）. Conclusions Rosiglitazone may inhibit high glucose induced NF-κB activation and ICAM-1 expression in mesangial cells. These findings may provide an experimental evidence for further evaluating the possibly protective effect of rosiglitazone against diabetic nephropathy.