单纯性肥胖大鼠心脏改变及保护

目的通过建立单纯性肥胖大鼠的动物模型,观察肥胖大鼠肾素—血管紧张素—醛固酮系统(RAAS)的改变、心脏结构的改变以及血管紧张素Ⅱ受体拮抗剂氯沙坦(losartan)对其的干预保护作用,并对其可能机制进行探讨。方法将25只雄性大鼠分为对照组和高脂组,高脂组又分为用药组和非用药组,检测肥胖大鼠血浆血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)水平,并对其心功能各项指标进行测定。通过病理切片观察两组大鼠的心脏结构变化。结果高脂非用药组AngⅡ、ALD比对照组升高,差异有统计学意义(P<0.05);左心室重量(LVW)、左心室重量与体重比值(LVWI)均大于对照组(P<0.05);高脂非用药组大鼠LVW、LVWI与高脂用药组相比差异有统计学意义(P<0.05)。相关分析显示AngⅡ、ALD均与LVW之间有正相关关系。结论①肥胖大鼠存在心肌肥厚,心脏舒张、收缩功能降低的心血管改变。②肥胖大鼠存在RAAS的异常激活。③小剂量ATI受体拮抗剂氯沙坦可预防和逆转左室肥厚,对心肌细胞有保护作用,可能通过抑制心肌ATI受体mRNA合成来实现。

Effects of obesity structure of rats and protective action of losartan

Objective This study was designed to investigate the effects of simple obesity on myocardial structure of rats and protective action of losartan(angiotensin Ⅱ receptor blocker) and to explore the possible mechanism.Method The obesity model induced by high fat feed was established, 25 rats were selected and randomized to two groups: normal control group and hyperlipidemia group;the hyperlipidemia group was divided into two groups ,including losartan group,non-medication group. The rats' angiotensin Ⅱ, aldosterone were measured.The indices of myocardial function were also measured .The changes of histology and pathology were observed by pathological section. Result Compared with normal control group, the obesity group had higher AngⅡ,ALD. AngⅡ and ALD both had positive correlation with LVW. The hyperlipidemia group had myocardium hypertrophy.Compared with non-medication group, losartan group was declined in LVW,LVWI. Conclusion Dysfunction of myocardial diastole and systole all presented in the obesity rats. Renin-angiotensin- aldosterone system(RAAS) was activated in obesity groups. The activated RAAS is the possible mechanism of the myocardial malfunction.The protective mechanism of losartan may be realized by inhibiting synthesis of ATI mRNA.