吡格列酮对胰岛素抵抗OLETF大鼠血清IL-18、TLR4表达的影响  

Effect of Pioglitazone on Interleukin-18 and Toll-Like Receptor 4 Expression in OLETF Rats with Insulin Resistance

作　　者：孙立亭[1] 赵志强[2] 田凤石[3] 

机构地区：[1]天津医科大学研究生院,300070 [2]天津医科大学第二医院 [3]天津市第四中心医院

出　　处：《天津医药》2014年第6期569-572,共4页Tianjin Medical Journal

摘　　要：目的研究吡格列酮对胰岛素抵抗(IR)自发性持续高血糖(OLETF)大鼠血清白细胞介素(IL)-18和Toll样受体4(TLR4)表达的影响及其降低心血管疾病风险的可能机制。方法 OLETF大鼠24只,高脂喂养20周建立IR模型,后随机均分为模型(M)组和吡格列酮(P)组,M组继续给予高脂饲料,P组给予吡格列酮加高脂饲料。另择LETO大鼠12只为正常对照(NC)组,给予标准饲料。药物干预20周后测定各组大鼠血清胰岛素(FINS)、空腹血糖(FBG)、IR指数(HOMA-IR)、胰岛素敏感指数(ISI)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、IL-18、TLR4水平。结果 24只OLETF大鼠均造模成功。M组FBG、FINS、HOMA-IR、TC、TG、LDL-C、IL-18和TLR4均高于NC组和P组,ISI、HDL-C均低于NC组和P组(均P<0.05)。血清IL-18与FBG、FINS、HOMA-IR、TLR4呈正相关,与ISI呈负相关。血清TLR4与FBG、FINS、HOMA-IR、IL-18呈正相关,与ISI呈负相关(均P<0.05)。多元Logistic回归分析结果显示IL-18、TLR4是HOMA-IR的影响因素。结论吡格列酮可改善OLETF大鼠的IR及炎症状态,其可能通过降低IL-18水平和抑制TLR4途径发挥抗炎作用,从而降低心血管疾病的发生风险。Objective To investigate change of TLR4 in OLETF （Otsuka Long-Evans Tokushima fatty） rats with in-sulin resistance （IR）, and to study the effect of pioglitazone （PIO） on the expression of TLR4, and to explore the possible mechanisms of the PIO reducing the risk of cardiovascular diseases. Methods Twenty four OLETF rats were fed with high-fat diet for 20 weeks to establish the IR model then they were randomly assigned into two groups：the model group （group M）, in which the rats were fed with high-fat diet;the PIO group （group P）, in which the rats were fed with PIO in addition to high-fat diet . Control group include 12 OLETF rats fed with normal diet （group NC）. After 20 weeks of drug intervention, plasma levels of FINS （Fasting INSulin）, FBG （Fasting Blood Glucose）, blood lipid, IL-18 and TLR4 were assessed in every group. Results Comparing with group NC, FBG, Blood lipid, IL-18 and TLR4 were significantly increased in group M（P〈0.05 or P〈0.01）, comparing with group M, FBG, Blood lipid were improved in group P, and serum IL-18, TLR4 were signifi-cantly lower in the group P than that in group M（P〈0.05 or P〈0.01）. Conclusion TLR4 may be involved in IR by pro-moting inflammatory response, and PIO can significantly improve IR and inflammatory, and reduce the risk of cardiovascular diseases by inhibiting the expression of TLR4.

关 键 词：胰岛素抵抗 白细胞介素18 Toll样受体4 心血管疾病 吡格列酮 INTERLEUKIN-18 TOLL-LIKE receptor 4 

分 类 号：R587.1[医药卫生—内分泌] R54[医药卫生—内科学]