罗格列酮改善胰岛素抵抗大鼠心肌脂联素及受体表达的研究

Rosiglitazone upregulates the expression of myocardial adiponectin and receptor 1 in insulin resistant rats

目的探讨罗格列酮对胰岛素抵抗大鼠心肌脂联素(APN)及其受体表达的影响。方法将30只雄性SD大鼠,随机分为3组:对照组10只,予普通饲料喂养8周;胰岛素抵抗组(IR组)10只,高果糖饮食喂养8周;罗格列酮组(RSG组)10只,高果糖饮食喂养8周+罗格列酮3mg/(kg·d)灌胃4周。所有大鼠喂养第8周末采血测定空腹血糖(FBG)、空腹胰岛素(FSI)水平,采用ELISA方法测量血清及心肌APN水平,采用RT-PCR方法测定心肌组织中APN受体mRNA表达情况。结果 IR组的FBG、FSI分别为(15.90±2.15)mmol/L、(19.82±4.04)mU/L,明显高于对照组的(5.85±0.78)mmol/L、(10.51±2.21)mU/L(P<0.01);胰岛素敏感指数(ISI)IR组为(-5.73±0.21),低于对照组(-4.09±0.24),P<0.01;血清APN为(3.90±0.87)μg/ml,低于对照组的(5.90±1.26)μg/ml。RSG组FBG为(11.68±2.24)mmol/L,FSI为(13.59±3.74)mU/L,明显低于IR组(P<0.01,P<0.05),ISI为-5.02±0.25,血清APN为(4.85±0.58)μg/ml,均明显高于IR组(P<0.05)。实验第8周末对照组、IR组、RSG组大鼠心肌APN分别为(0.19±0.03)、(0.12±0.02)、(0.16±0.03)μg/mg,AdipoR1mRNA表达水平分别为0.31±0.06、0.21±0.06、0.26±0.05,IR组及RSG组显著低于对照组(P<0.05),RSG组显著高于IR组(P<0.05);AdipoR2组间差异无统计学意义。结论 RSG能够增加IR大鼠胰岛素敏感性,增加循环中APN水平,提高心肌APN及其AdipoR1表达,产生心肌保护作用。

Objective To explore the effect of rosiglitazone on the expression of myocardial adiponectin and its re-ceptors in insulin resistant rats. Methods Thirty male SD rats were randomly allocated into three groups： （1） the control group, which were fed with ordinary diet for 8 weeks; （2） the IR group, which were fed with high fructose diet and were treated with 0.9% saline for the next 4 weeks; （3） the RSG group, which were fed with high fructose diet and treated with rosiglitazone 3 mg/（kg＂ d） for the next 4 weeks. After 8 weeks, the blood sample was obtained for measuring Fasting Blood Glucose （FBG）, Fasting Serum Insulin （FSI）. Serum and myocardial APN were measured using ELISA method. The mRNA expressions of myocardial AdipoR1,AdipoR2 were detected by RT-PCR. Results Compared with the control group, serum APN and ISI decrease were accompanied with increase in levels of FBG, FSI in the IR group. Compared with the IR group, serum APN, ISI increase were accompanied with decrease in levels of FBG, FSI in the RSG group. Protein expression of myocardial APN and mRNA expression of AdipoR1 decreased in the IR group compared with the control group. Protein expression of myocardial APN and mRNA expression of AdipoR1 were enhanced by the treatment of RSG. Conclusion Rosiglitazone can upregulate the myocardial expression of adiponectin and AdipoR1 through activating PPAR% which is the possible mechanism of its cadioprotective effect.