TLR4与胰岛素抵抗小鼠主动脉炎性细胞因子表达  

Effect of TLR4 on expression of inflammatory cytokine in aortic artery in mice with insulin resistance

作　　者：饶小娇 于曼丽[1] 朱晓波[1] 郝敏[1] 常晓彤[1] 

机构地区：[1]河北北方学院临床检验诊断学重点实验室,河北张家口075000

出　　处：《中国公共卫生》2016年第11期1480-1484,共5页Chinese Journal of Public Health

基　　金：河北省自然科学基金(C2011405015);河北北方学院创新人才培育项目(CXRC1316)

摘　　要：目的探讨Toll样受体4(TLR4)对小鼠胰岛素抵抗的作用及对主动脉炎性细胞因子的影响。方法选取出生21 d雄性C57BL/6小鼠45只,随机分为3组,每组15只,对照组(基础饲料)、高脂对照组和TAK-242组(给予高脂饲料);7个月后,行葡萄糖耐量试验(GTT)和胰岛素耐量试验(ITT);TAK-242组(胰岛素抵抗小鼠)给予TLR4抑制剂TAK-242干预5个月,采血进行GTT和ITT后,处死小鼠,收集血清和主动脉组织标本;采用实时荧光定量PCR方法检测小鼠主动脉组织TLR4的表达及其下游肿瘤坏死因子α(TNF-α)和白细胞介素-6(IL-6)含量;采用全自动生化分析仪测定血清总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和甘油三酯(TG)含量。结果与对照组比较,高脂组小鼠在高脂饲喂3个月后体重明显升高,7个月后小鼠调节血糖能力受损,胰岛素敏感性降低;TAK-242干预5个月后,与高脂对照组比较,TAK-242组小鼠葡萄糖调节能力和胰岛素敏感性均有所改善;与对照组比较,高脂对照组与TAK-242组小鼠血清中TG、TC、LDL-C、HDL-C水平均明显升高(P<0.05);高脂对照组与TAK-242组小鼠血清中TG、TC、LDL-C和HDL-C水平无明显差异;实时荧光定量PCR结果显示,高脂对照组小鼠主动脉组织中TLR4、TNF-α和IL-6表达水平[分别为(1.91±0.32)、(2.71±0.52)、(3.24±0.41)]与对照组比较[分别为(1.00±0.20)、(1.00±0.17)、(1.00±0.23)]明显升高(P<0.01);与高脂对照组比较,TAK-242组小鼠主动脉组织中TLR4、TNF-α和IL-6表达水平[分别为(1.23±0.27)、(1.93±0.35)、(1.67±0.30)]均下调(P<0.05)。结论高脂饮食可诱导小鼠胰岛素抵抗;胰岛素抵抗状态下,主动脉炎症的发生可能与TLR4信号通路活化有关。Objective To investigate the role of Toll-like receptor （ TLR4 ） in insulin resistance and the effect of TLR4 on inflammatory cytokine expression in aortic artery in mice with insulin resistance （IR）. Methods Forty-five male C57BL/6 mice （21 days old） were randomly divided into three groups （15 in each group） ：a control group fed with basic diet （low fat diet,LFD） ,a high fat diet control group （HFD-C）and a TAK-242 treatment group （HFD-T） both fed with high fat diet. Seven months after the treatments, glucose tolerance test （GTT） and insulin tolerance test （ITT） were performed in all the mice. After the establishment of IR model ,the mice of HFD-T group were injected intra- peritoneally with TLR4 inhibitor TAK-242 twice a week for five consecutive months. All the mice were sacrificed and their serum and aortic artery tissue samples were collected after underwent GTT and ITT by the end of the treatments. The expressions of TLR4, tumor necrosis factor ~x （TNF-ct） and interleukin-6 （ IL-6 ） in aortic artery tissue were determined using real-time quantitative PCR（RT-PCR）. Automatic biochemical analyzer was used to detect serum total cholesterol （ TC ）, high-density lipoprotein cholesterol （ HDL-C ）, low-density lipoprotein cholesterol （ LDL-C ）, and triglyceride （TG） levels. Results Compared with the mice of LFD group, those of HFD group showed significantly higher body weight （ 30. 05 ±1.67 vs. 28.29 ±1.30 grams, P 〈 0. 05 ）, impaired glucose regulation, and decreased insulin sensitivity seven months after the treatment;five months after the TAK-242 intervention, the glucose tolerance and insulin sensitivity of HFD-T group were improved compared with those of the HFD-C group. The serum TG, TC, LDL-C, and HDL-C were significantly increased in the mice of HFD-T and HFD-C group compared to those in the mice of LFD （ P 〈 0. 05 for all） ;however, there were no significant differences in serum TG, TC, LDL-C, and HDL-C between HFD-T and HFD-C g

关 键 词：高脂饮食 胰岛素抵抗 Toll样受体4(TLR4) 主动脉组织 肿瘤坏死因子α(TNF-α) 白细胞介素-6(IL-6) 

分 类 号：R392[医药卫生—免疫学]