罗格列酮对胰岛素抵抗大鼠胰腺组织NF—κB及MCP-1表达的抑制作用

Inhibitory effects of rosiglitazone on activation of NF-κB and expression of MCP-1 in pancreas of insulin resistant rats

目的观察罗格列酮对高脂饮食诱导的实验性胰岛素抵抗大鼠胰腺组织NF-κB和MCP-1的表达水平的影响，从而探讨罗格列酮的抗炎机制。方法 将34只清洁级近交系雄性SD大鼠分为正常对照组（NC组，10只），单纯高脂喂养组（HF组，12只），高脂饮食＋罗格列酮干预组（HFR组，12只）。17周后，应用Western印迹方法检测肾组织NF—κB p65的含量；免疫组化SP法检测MCP-1的表达。结果与A组相比，HF组及HFR组NF—κB在肾脏组织的含量均明增高，且差异有统计学意义（P〈0．01）。与HF组相比，罗格列酮处理后，NF-κB的表达明显下调（P〈0．01）。MCP-1在各组的表达的变化与NF—κB的趋势相同。结论高脂饮食可诱导正常大鼠NF-κB以及其下游的分子MCP-1在胰腺中的高表达，罗格列酮可减少NF-κB和MCP-1的高表达，提示抗炎治疗对延缓糖尿病的发展有一定的作用。

Objective To investigate the effects of rosiglitazone on activation of nuclear factor-kappa B （NF-κB） and the expression of monocyte chemoattractants protein-1 （ MCP-1 ） in the pancreas of high-fed-diet rats with insulin resistance and the mechanism of anti-inflammatory of rosiglitazone. Methods 34 Male SD rats were divided into3 groups： normal control （NC, n = 10）, high-fat diet group （HF n = 12） and the high-fat diet plus rosiglitazone-treatment group （HFR, n = 12）. At the end of the 17th week, pancreas tissues were taken out from rats for the measurement of expression of NF-κB P65 protein and MCP-1. Results The expression of NF-κB p65 protein and MCP- 1 in HFR and HF was significantly higher than that in NC （ P 〈 0. 01 ）. The treatment with rosiglitazone significantly decreased the enhanced expression of NF-κB p65 protein and MCP-1 by these two factors （HFR vs HF, P 〈0.01 ）, although the expression of NF-κB P65 and MCP-1 was in HFR still higher than that in NC （ P 〈 0. 01 ）. Condusion High-fat diet up-regulate the expression of NF-κB and MCP- 1 in pancreas of high-fed-diet rats with insulin resistance rat. Rosiglitazone can partly inhibit this increasing expression. Anti-inflammatory effect of rosiglitazone will he helpful to prevent the development of diabetic mellitus.