罗格列酮对胰岛素抵抗大鼠内脏脂肪组织TNF-α表达的影响

Effects of rosiglitazone on the expression of TNF-α in visceral adipose tissue of insulin-resistant rats

目的研究罗格列酮对高糖膳食诱导的胰岛素抵抗(IR)大鼠内脏脂肪组织肿瘤坏死因子-α(TNF-α)表达的影响。方法高糖膳食喂养SD大鼠6周复制非肥胖胰岛素抵抗大鼠模型。建模成功后,将IR大鼠随机分为胰岛素抵抗组(IR组)和罗格列酮组(ROS组),每组10只。取普通饲料喂养的大鼠作为对照组(CN组,n=10)。从第7周开始,ROS组给予罗格列酮10μmol/(kg.d)灌胃,持续6周,CN组和IR组给予等量蒸馏水灌胃。于实验的第6和第12周检测大鼠收缩压、体重和血生化指标(空腹血糖、餐后2h血糖、胰岛素、游离脂肪酸、甘油三酯、高密度脂蛋白胆固醇),并计算胰岛素抵抗指数(HOMA-IR)。于实验的第12周末,取大鼠皮下、内脏脂肪组织,计算脂体比,采用免疫组化法和RT-PCR法检测TNF-α的表达。结果与CN组比较,IR组的收缩压、HO-MA-IR、血清胰岛素、甘油三酯、游离脂肪酸水平升高,高密度脂蛋白胆固醇水平降低(P<0.01)。与IR组比较,ROS组除高密度脂蛋白胆固醇水平升高以外,前述各项指标均降低(P<0.01)。三组大鼠空腹血糖和餐后2h血糖均在正常范围,且三组的体重和脂体比无统计学差异(P>0.05)。免疫组化检测显示,TNF-α表达于内脏脂肪组织的细胞间质,脂肪细胞本身未见TNF-α表达。IR组脂肪组织TNF-α蛋白及mRNA表达水平显著高于CN组和ROS组(P<0.01),后两组间比较无统计学差异(P>0.05)。结论罗格列酮能明显减轻高糖膳食诱导的非肥胖IR大鼠的IR状况及血脂、血压异常,并能抑制内脏脂肪组织细胞间质TNF-α的过度表达。

Objective To explore the effects of rosiglitazone on the expression of TNF-α in visceral adipose tissue of insulin-resistant rats induced by high-glucose diet. Methods Sprague-Dawley （SD） rats were fed with high-glucose diet for 6 months to reproduce the non-obesity insulin-resistant rat model （abbreviated as IR rats）. The model rats were then randomized into insulin resistan （IR） group and rosiglitazone （ROS） group （10 each）. Ten rats fed with normal diet were enrolled as controls （CN group）. Rats in ROS group were administered with 10μmol/（kg·d） of rosiglitazone for 6 weeks from the 7th week of experiment,and those in CN and IR groups were administered with same amount of distilled water. At the 6th and 12th week,the systolic pressure,body weight,and biochemical parameters （fasting and 2-hour post-glucose load plasma glucose,insulin,free fatty acid,triglyceride,high density lipoprotein cholesterol） were measured,and insulin resistance index （HOMA-IR） was calculated. At the end of the 12th week,the visceral adipose tissue was collected to calculate the ratio of visceral fat to body weight （VF/BW）,and to determine the protein and mRNA expressions of tumor necrosis factor-α （TNF-α） with inmmunohistochemical assay and RT-PCR. Results As compared with CN group,the systolic pressure,HOMA-IR,plasma insulin,triglyceride and free fatty acid increased,whereas high density lipoprotein cholesterol decreased （P0.01） in IR group. As compared with IR group,all the above parameters,except high density lipoprotein cholesterol,decreased in ROS group （P0.01）. The levels of fasting and 2-hour post-glucose load plasma glucose in all the 3 groups maintained within normal range,and no significant difference in body weight and VF/BW was found among the 3 groups （P0.05）. Inmmunohistochemical examination showed positive expression of TNF-α in intercellular substance,but not in visceral adipocytes. The expressions of TNF-α protein and mRNA in visceral adipose tissue were dramatically higher in IR group than in CN and ROS groups （P0.01）,while no significant difference was found between the latter 2 groups （P0.05）. Conclusion Rosiglitazone may significantly abate insulin resistance,reduce the abnormality of plasma lipid and blood pressure,and inhibit the over expression of TNF-α in visceral adipose tissue in the non-obesity insulin-resistant rats induced by high-glucose diet.