罗格列酮和厄贝沙坦对高胆固醇血症大鼠血脂及心肌脂联素的干预作用

Effects of rosiglitazone and irbesartan on lipid profile and myocardial adiponectin level in rat model with hypercholesterolemia

目的探讨高胆固醇血症大鼠血脂和心肌脂联素水平的变化及罗格列酮和厄贝沙坦的干预作用。方法采用高脂饮食建立高脂血症动物模型,36只雄性Wistar-Kyoto大鼠,随机分为普通饲料组(Con组,n=6)、高脂饲料组(Cho组,n=10)、高脂饲料+罗格列酮组(Ros组,n=10,4mg·kg^(-1)·d^(-1))、高脂饲料+厄贝沙坦组(Irb组,n=10,50 mg·kg^(-1)·d^(-1))。各药物组在高脂饲养1 mo后开始药物干预,持续5 mo。观察血脂、心肌组织脂联素、血管紧张肽Ⅱ和心肌组织形态学变化。结果高脂饲料饲养6 mo后,Cho组三酰甘油、胆固醇、低密度脂蛋白均明显高于Con组(P<0.01);罗格列酮和厄贝沙坦能显著降低高脂饲养诱发大鼠三酰甘油和胆固醇水平的升高(P<0.01);罗格列酮能显著降低低密度脂蛋白水平(P<0.01),而厄贝沙坦对低密度脂蛋白水平没有影响;罗格列酮与厄贝沙坦均可明显抑制高脂饮食诱发的心肌局部脂联素水平的下降和心肌局部血管紧张肽Ⅱ浓度的升高(P<0.01);形态学观察显示Cho组心肌组织可见明显的脂质沉积,罗格列酮与厄贝沙坦明显抑制这一病理改变。结论罗格列酮和厄贝沙坦均能通过改善脂质代谢、升高心肌组织脂联素水平、降低心肌局部血管紧张肽Ⅱ浓度,拮抗高脂饲养诱发心肌形态学的异常,从而发挥心肌保护作用。

AIM To investigate the effects of rosiglitazone and irbesartan on blood lipids, myocardial adiponectin in rat model with hypercholesterolemia. METHODS Rat model with hypercholesterolemia was developed by a cholesterol-rich diet. Thirty-six male Wistar-Kyoto rats （body weights ranged from 180 to 250 g） were randomized into four groups. The control group （Con group, n = 6） was fed a regular diet, the cholesterol-rich diet group （Cho group, n = 10） was fed a cholesterol-rich diet, the group on rosiglitazone treatment （Ros group, n = 10） was fed a cholesterol-rich diet plus rosiglitazone （4 mg·kg^-1·d^-1） , and the group on irbesartan treatment （Irb group, n = 10） was fed a cholesterol-rich diet plus irbesartan （50 mg·kg^-1·d^-1）. At the end of 6 mo, angiotensin Ⅱ in myocardium and plasma, serum lipid concentrations and myocardial adiponectin levels were measured by radioimmunoassay, respectively. Morphology change was observed by Hematoxylin and eosin stain. RESULTS After 6 mo, Serum TC, TG, and LDL levels in Cho group were significantly higher than Con group （P 〈 0.01 ）. The increases in TC and TG levels were significantly suppressed by rosiglitazone and irbesartan compared with Cho group （P 〈 0.01 ）. There was clear suppression of the increase in LDL level in the Ros group （P 〈 0.01）, while there was not affected in the Irb group. Moreover, both rosiglitazone and irbesartan markedly suppressed the decrease in myocardial adiponectin level and the increase in myocardial angiotensin Ⅱ evoked by the cholesterol-rich diet. Excessive lipid deposits in cardiomyocytes were observed in the rats fed on a cholesterol-rich diet, while this characteristic alteration induced by the cholesterol-rich diet was significantly suppressed to equal extents by rosiglitazone and irbesartan. CONCLUSION Rosiglitazone and irbesartan could suppress the myocardial morphological abnormality evoked by cholesterol-rich diet, and exert myocardial protective action via the improvement of lipid metabolism, the increase in local myocardial adiponectin level and the reduction in myocardial angiotensin Ⅱ concentration in the rat model with hypercholesterolemia.