血管紧张素(1-7)对不同模型高血压大鼠左心室结构的影响

Effect of angiotensin( 1 -7) on left ventricular hypertrophy and myocardial fibrosis in 2K1C and INAC hypertensive models

目的探讨血管紧张素(1-7)[Ang(1-7)]对单纯压力负荷增加及肾素-血管紧张素-醛固酮系统(RAAS)激活的高血压模型左心室肥厚及心肌纤维化的影响及其机制。方法建立二肾一夹(2K1C)及肾下主动脉缩窄(INAC)模型,应用微渗泵植入技术,使Ang(1-7)进行不同时间(14、28d)的体内干预,采用定性及定量分析的方法检测Ang(1-7)对这2种高血压模型早期(14d)和晚期(42d)左心室心肌细胞及纤维化程度的影响。结果对2K1C和INAC动物模型,早期其左心室质量(LVW)、左心室质量指数(LVI)及左心室心肌细胞横断面积(LCA)均较对照组明显增加(P<0.05),晚期上述指标增加更为显著(P<0.01);Ang(1-7)可使2K1C动物模型的上述指标均显著下降(P<0.05),但对INAC动物模型,Ang(1-7)使其上述指标在早期显著下降(P<0.05),晚期略有下降(P>0.05)。对2K1C动物模型,早期已出现明显的心肌纤维化(P<0.05),晚期更为显著(P<0.01);Ang(1-7)可明显抑制早期的间质及血管周围纤维化(P<0.05),在晚期,Ang(1-7)可明显抑制血管周围纤维化(P<0.05),但对间质纤维化,虽有下降趋势,但不明显(P>0.05)。对IN-AC动物模型,早期心肌纤维化并不显著(P>0.05),晚期则有明显表现(P<0.05),Ang(1-7)可有效抑制间质和血管周围纤维化(P<0.05)。结论Ang(1-7)可预防改善这2种高血压模型的左心室肥厚和心肌纤维化,但对2种模型不同时期的改善程度不同,提示Ang(1-7)可能具有不同的作用机制。

Obiective To determine the effect ofangiotensin（1-7） [Ang（1-7） J on the left ventricular hypertrophy and myocardial fibrosis in a pressure-overload hypertensive models, infra-nephrie aorta coarctation （INAC）, and a renin-angiotensin-aldosterone system （RAAS） activation hypertensive model, two kidney one clip （2K1C） in the early and late stage. Methods Totally 120 health male Wistar rats were randomly and equally divided into 6 groups, that is, sham INAC group, INAC group, INAC Ang（1-7） group, sham 2KIC group, 2K1C group and 2K1C Ang（ 1 -7） group. INAC and 2K1C hypertensive models was established to corresponding groups and osmotic minipump implantation was carried out to the rats to deliver the Ang（ 1 -7 ） to their body homogenously and to examine the parameters representing the blood pressure, including left ventricular hypertrophy （LVW, LVI, CA） and myocardial fibrosis （CVF and PVCA）. Results Left ventricular hypertrophy （LVH） was observed in the early stage and developed in the late stage both in the 2K1C and INAC groups. Ang（ 1 -7） decreased LVW, LVI, CA both in the early and late stage in the 2K1C model（P 〈0. 05）. But to INAC model, Ang （ 1 - 7 ） only decreased the pressures in the early stage （P 〈 0.05）, but not in the late stage（P 〉 0. 05）. Myocardial fibrosis happened and developed progressively in the 2K1C hypertensive model （P 〈 0. 05）. Ang（ 1 -7） was able to alleviate interstitial as well as perivascular fibrosis as used in the early stage （P 〈 0. 05 ）, while it only alleviated perivascular fibrosis in the late stage （ P 〈 0. 05 ）, had no marked effect on the interstitial fibrosis（P 〉0. 05）. There was a mild myocardial fibrosis happened in the left ventricle of the INAC model in the late stage（P 〈0. 05）, and Ang（ 1-7） was able to alleviate both interstitial and perivaseular fibrosis effectively（P 〈 0. 05）. Conclusion Ang （1 -7 ） can effectively prevent and improve left ventricular hypertrophy and myocardial fibrosis, but in the different stage, it exerts different effect, which indicate there are multiple mechanisms of Ang（1 -7） .