天津医药

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PIO对胰岛素抵抗OLETF大鼠血清IL-18、TLR4表达的影响

孙立亭1,赵志强2,田凤石3   

  1. 1. 天津医科大学
    2. 天津医科大学第二医院
    3. 天津市第四中心医院
  • 收稿日期:2014-01-24 修回日期:2014-03-05 出版日期:2014-06-15 发布日期:2014-06-15
  • 通讯作者: 孙立亭

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

  • Received:2014-01-24 Revised:2014-03-05 Published:2014-06-15 Online:2014-06-15

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摘要： 【摘要】 目的 研究过氧化物酶体增殖物激活受体（PPAR-γ）激动剂吡格列酮对胰岛素抵抗(IR)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）、甘油三酯(TG)、总胆固醇（TC）、高密度脂蛋白（HDL-C）、低密度脂蛋白（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。

关键词: 胰岛素抗药性, 白细胞介素18, Toll样受体4, 心血管疾病, 大鼠, 近交OLETF, 吡格列酮

Abstract: [Abstract] Objective To investigate change of TLR4 in OLETF rats with insulin resistance(IR), and study the effect of peroxisome proliferator-activated receptor γ（PPAR-γ）pioglitazone (PIO) on the expression of TLR4, and the possible mechanisms of the PIO reducing the risk of cardiovascular diseases. Methods: 24 OLETF rats were fed with high-fat diet for 20 weeks to establish the IR model. 24 OLETF rats with IR 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 high-fat diet and PIO. 12 LETO rats fed with normal diet were served as normal control group (group NC). After 20 weeks of drug intervention, the plasma levels of FINS, FBG, blood lipid, IL-18 and TLR4 were detected in every group. Results Comparing with group NC, the FBG, Blood lipid, IL-18 and TLR4 were significantly increased in group M（P<0.05 or P<0.01）; comparing with group M, the FBG, Blood lipid were improved in group P, and The serum IL-18,TLR4 were significantly lower in the group P than that of group M（P<0.05 or P<0.01）. Conclusion TLR4 may be involved in IR by promoting inflammatory response, and PIO can significantly improve IR and inflammatory stage, and reduce the risk of cardiovascular diseases by inhibiting the expression of TLR4.

Key words: insulin resistance, interleukin-18, toll-like receptor 4, cardiovascular diseases, rats, inbred OLETF, pioglitazone