罗格列酮对2种高血压大鼠的降压作用及机制

The anti-hypertensive effect of insulin sensitizer rosiglitazone in two sorts of hypertensive rat

目的观察胰岛素增敏剂罗格列酮(rosiglitazone,RSG)对胰岛素抵抗高血压大鼠及两肾一夹肾血管性高血压大鼠血压的影响,探讨其作用机制。方法用10%果糖水喂养雄性SD大鼠制备胰岛素抵抗高血压大鼠(insulin resistance hypertensive rat,IRHR)模型,同时用两肾一夹法制备肾血管性高血压大鼠(two-kidney,one-clipped renovascular hypertensive rat,RHR)模型,观察RSG对2组大鼠的降压作用,通过检测空腹血糖(fastingblood glucose,FBG)、空腹胰岛素(fasting serum insulin,FINS)、瘦素(leptin,LP)、甘油三酯(triglyceride,TG)及计算胰岛素敏感性指数(insulin sensitivity index,ISI)等指标,从胰岛素抵抗(insulin resistance,IR)/高胰岛素血症(hy-perinsulinemia,HIS)角度探讨RSG可能的降压机制。结果RSG处理后IRHR组大鼠收缩压(systolic blood pres-sure,SBP)、FINS、LP和TG与处理前相比明显降低,ISI明显升高(P<0.01),FBG无明显改变(P>0.05)。RSG处理后RHR组大鼠与处理前相比SBP、FINS、LP、TG、ISI和FBG与RHR组相比无明显变化(P>0.05)。结论RSG可明显降低IRHR模型的血压而对RHR模型无明显降压作用。其机制主要通过改善IR/HIS以及高LP血症起降血压作用。

Objective To observe the anti - hypertensive effect of insulin sensitizer rosiglitazone （RSG） on the models of insulin resistance hypertensive rat （IRHR） and two - kidney, one - clipped renovascular hypertensive rat （ RHR）, and to study the antihypertensive mechanism of RSG. Methods The model of IRHR was established by feeding standard fodder and 10% fructose water, while the model of two - kidney, one - clipped RHR was formed by constricting the left kidney artery. The anti - hypertensive mechanism of RSG was studied by examining the ratio of insulin resistance / hyperinsulinemia （IR/HIS） and by measuring systolic blood pressure （SBP）, fasting blood glucose （FBG）, fasting serum insulin （FINS）, leptin （LP）, triglyceride （TG） and calculating insulin sensitivity index （ISI）. Results As compared with that in the IRHR group at the end of experiment, in the RSG treated IRHR group, the levels of SBP, LP, FINS and TG were decreased obviously, the level of ISI was increased obviously （ P 〈0. 01 ）, but the level of FBG was not changed significantly （ P 〉0.05）. When comparison was made between the two RHR groups, no significant changes were found in the levels of SBP, LP, FINS, TG, ISI and FBG after RSG treatment （ P 〉0.05）. Conclusion RSG has an obvious anti - hypertensive effect on IRHR, but not on RHR. The results suggest the mechanism of anti - hypertensive effect of RSG is indirectly through the improvement of IR/HIS and high LP.