阿昔莫司对2型糖尿病合并高脂血症大鼠肝脏脂质代谢及炎症反应的影响

Effect of acipimox on liver lipid metabolism and inflammation in type 2 diabetic rats with hyperlipidemia

目的观察阿昔莫司对2型糖尿病合并高脂血症大鼠肝脏脂质代谢及炎症反应的影响。方法选择8周龄雄性Goto-Kakizaki(非肥胖型2型糖尿病)大鼠50只,将其随机分为5组,每组10只。正常对照组给予正常饮食,其余组给予高脂饮食(猪油18%、蔗糖20%、蛋黄3%、基础饲料59%),8周后低、中、高剂量组分别给予阿昔莫司灌胃,每天1.5、3、10 mg/kg;正常对照组及模型组给予同体积生理盐水灌胃。各组均干预2周。记录各组体质量、肝脏占体质量比例及食物消耗量;各组于末次给药后禁食12 h进行葡萄糖耐量试验,测空腹血糖(FPG),以葡萄糖负荷后60 min血糖为糖耐量值,以葡萄糖负荷后3~15 min血糖下降速率为胰岛素敏感指数,用稳态模型计算胰岛素抵抗指数(HOMA-IR);检测各组血清及肝组织脂质水平;用ELISA法检测肝组织中CRP、TNF-α、IL-6,用ELISA-Phoenix法检测肝组织脂联素。结果与正常对照组比较,模型组肝脏占体质量比例高;FPG、糖耐量值、HOMA-IR高,胰岛素敏感指数低;血清TC、TG、游离脂肪酸水平高及HDL-C水平低,肝组织TC、TG高;肝组织CRP、TNF-α、IL-6、脂联素水平高(P均<0.05)。与模型组比较,低、中、高剂量组以上指标均改善;中、高剂量组肝脏占体质量比例、FPG、HOMA-IR、血清HDL-C、血清游离脂肪酸、肝组织TC、TG及肝组织TNF-α、IL-6、脂联素,高剂量组糖耐量值、胰岛素敏感指数、血清TC、血清TG、肝组织CRP与模型组比较差异均有统计学意义(P均<0.05)。结论阿昔莫司可改善2型糖尿病合并高脂血症大鼠的肝脏脂质代谢紊乱,减轻其肝脏炎症反应。

Objective To observe the effect of acipimox on liverlipid metabolism and inflammation in type 2 diabetic rats with hyperlipidemia.Methods Fifty 8-week-old male Goto-Kakizaki rats with type 2 diabetes(non-obesity diabetes)were randomly divided into five groups.The rats in the control group were given normal diet,and the rats in the other four groups were given high-fat diet(lard 18%,sucrose 20%,egg yolk 3%,basal feed 59%).After 8 weeks,the rats in the low-dose,medium-dose and high-dose groups were given acipimox 1.5,3 and 10 mg/kg per day by gavage,while rats in the control group and model group were given the same volume of normal saline by gavage.All groups were treated for 2 weeks.Body weight,proportion of liver to body weight and food consumption were recorded.Glucose tolerance test and fasting plasma glucose(FPG)of each group were detected after 12-hour fasting.The homeostasis model assessment of insulin resistance(HOMA-IR)was calculated with a steady-state model.The serum and liver lipids of each group were detected.ELISA was applied to detect the C-reaction protein(CRP),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6),and ELISA was applied to detect adiponectin.Results Compared with the control group,the proportion of liver to body mass was higher;FPG,glucose tolerance,HOMA-IR were higher,and insulin sensitivity index was lower;the levels of serum total cholesterol(TC),triglyceride(TG)and free fatty acid were higher,the levels of high-density lipoprotein cholesterol(HDL-C)were lower,and the levels of cholesterol and TG were higher in the liver tissues;the levels of CRP,TNF-α,IL-6 and adiponectin in the liver tissues were higher in the model group(all P<0.05).Compared with the model group,the indexes of low-dose,medium-dose and high-dose groups were all improved.There were significant differences in the proportion of liver to body weight,FPG,HOMA-IR,serum HDL-C,serum free fatty acid,liver cholesterol,TG and TNF-α,IL-6,and adiponectin in the liver tissues between the medium-dose and high-dose groups(all P<0.05).There were significant differences in glucose tolerance value,insulin sensitivity index,serum total cholesterol,serum triglyceride and CRP of liver tissue between the high-dose group and model group(all P<0.05).Conclusion Acipimox can improve the liver lipid metabolism disorder and reduce liver inflammation in type 2 diabetes mellitus rats with hyperlipidemia.