吡格列酮对胰岛素抵抗大鼠血浆同型半胱氨酸水平的影响

The impact of pioglitazone on plasma homocysteine high-fat diet-induced insulin resistance in rats

目的 研究吡格列酮对高脂饮食诱导的胰岛素抵抗大鼠血浆同型半胱氨酸 (Hcy)水平的影响。方法 将 2 4只Wistar大鼠随机分为 3组 :对照组给予普通饲料喂养 ;高脂组喂高脂饲料诱导胰岛素抵抗动物模型 ;盐酸吡格列酮组在喂饲高脂饲料的同时 ,灌胃给盐酸吡格列酮 10mg·kg-1·d-1。各组喂食 11周时 ,分别做空腹血糖、葡萄糖耐量试验和胰岛素耐量试验后处死动物。测定血糖和胰岛素水平 ,用HOMA模型公式计算胰岛素抵抗指数 (HOMAIR)。喂食 11周后测定血浆Hcy水平。结果 试验后 3组间体重变化、空腹胰岛素、空腹血糖、HOMAIR均有显著差异 (P <0 0 5 )。其中吡格列酮组空腹胰岛素、空腹血糖、HOMAIR均显著低于高脂组 (P <0 0 1)。试验后 3组间血浆Hcy也有显著差异 ,高脂组 (35 7± 14 1) μmol/L高于对照组 (9 95± 2 4 0 ) μmol/L和吡格列酮组 (8 8± 1 39) μmol/L。相关分析显示血糖曲线下面积、空腹胰岛素、空腹血糖、HOMAIR、内脏脂肪含量均与血浆Hcy水平显著相关 (P <0 0 5 )。进一步多元逐步回归分析显示仅空腹血糖 (r =0 5 0 4 ,P =0 0 31)和HOMAIR与血浆Hcy相关 (r=0 30 2 ,P =0 0 4 6 )。结论 高脂诱导的胰岛素抵抗与大鼠血浆Hcy水平升高有关 。

Objective To study the effect of pioglitazone on plasma homocysteine in insulin resistant rats induced by high fat diet. Methods 24 Wistar rats were randomized into 3 groups : a control group ( n =8) was fed with normal feeds. High fat diet was given to a high fat group and a pioglitazone group. Pioglitazone (10 mg/kg) was then administered by gavage daily for 11 weeks to the pioglitazone group. At week 11, glucose tolerance test was performed, and serum insulin, fasting glucose and plasma homocysteine were detected. Visceral adipose was weighted and then the ratio of visceral adipose over body weght calculated. Results Fasting glucose, fasting insulin, insulin resistance index (HOMA IR), and the visceral adipose were significantly different among the 3 groups. Fasting glucose, fasting insulin, HOMA IR, and visceral adipose were all significantly lower in the pioglitazone group than those in the high fat group ( P < 0 01). Plasma homocysteine decreased significantly in the pioglitazone treated rats[(8 8±1 39)μmol/L] as compared with the other two groups [control group: (9 95±2 40)μmol/L and high fat group: (35 7±14 1)μmol/L]. Correlation analysis showed that fasting glucose, fasting insulin, HOMA IR and visceral adipose were all factors influencing the plasma homocysteine. Stepwise regression test showed only fasting glucose( r =0 504, P =0 031) and HOMA IR ( r =0 302, P =0 046) independently affected the level of plasma homocysteine. Conclusion It is concluded that pioglitazone can lower plasma homocysteine in insulin resistant Wistar rats induced by high fat diet.