【摘要】 目的探讨血管紧张素-(1-7)[Ang-(1-7)]对野百合碱(MCT)诱导的肺动脉高压及右心室重构的影响.方法雄性SD大鼠30只,随机分为:正常对照组、MCT组、Ang-(1-7)组.MCT组和Ang-(1-7)组一次性颈部注射MCT 60 mg/kg,24 h后经微泵持续泵入生理盐水或Ang-(1-7)24μg/(kg.h).对照组一次性颈部注射相同体积的生理盐水,24 h后泵入生理盐水.经微泵泵入生理盐水或Ang-(1-7)4周后,通过彩色多普勒检测右心室游离壁厚度(RVFWT)、肺动脉加速时间(PAAT)和有无三尖瓣反流.监测大鼠血流动力学指标:右室收缩压(RVSP)、平均动脉压(MAP)和心率(HR).计算大鼠右心室肥厚指数(RVHI)和右心室体重指数(RVMI)的变化.通过HE染色观察肺动脉和右心室的病理变化,测定肺小动脉管壁厚度(WT)占动脉外径(ED)的百分比(WT%)及管壁面积(WA)占血管总面积的百分比(WA%).结果野百合碱诱导4周后,MCT组与对照组相比,RVSP、RVHI、RVMI、WT%、WA%和RVFWT显著升高,PAAT显著降低,部分大鼠出现三尖瓣反流.Ang-(1-7)组上述指标与对照组相比无明显的差异,未出现三尖瓣反流.病理切片显示:MCT组出现大鼠右室心肌肥大,心肌纤维化.Ang-(1-7)组心肌无明显病理改变.结论 MCT诱导的肺动脉高压模型中,早期给予Ang-(1-7)进行干预,能够逆转大鼠肺动脉压的升高和右心室重构.更多还原

【Abstract】 Objective To investigate the therapeutic effects of Ang-(1-7) on pulmonary hypertension and right ventricular remodeling in monocrotaline-treated rats.Methods Thirty SD rats were randomly divided into three groups: control group,MCT group and Ang-(1-7) group.Rats in MCT group and Ang-(1-7) group received 60mg/kg MCT injection subcutaneously and after 24 hours received either saline or 24ug/kg/h of Ang-(1-7) injection via osmotic minipumps for four weeks.The rats in control group were firstly injected saline subcutaneously and then received saline injection via osmotic minipumps for four weeks.Right ventricular free wall thickness(RVFWT),pulmonary arterial acceleration time(PAAT) and tricuspid regurgitation were measured by echocardiography.Right ventricular systolic pressure(RVSP),mean arterial pressure(MAP) and heart rate(HR) were measured.The animals’ hearts were measured to calculate the ratio of right ventricle to left ventricle plus septum(RVHI=RV/LV+S) and right ventricle mass to body weight(RVMI=RV/BW).Histopathological changs of lung and right ventricle were observed by hematoxylin and eosin staining.Percentage of wall thickness(WT%) and percentage of wall area(WA%) of pulmonary arterioles were evaluated.Restults Four weeks after monocrotaline injection,compared with control group,RVSP,RVHI,RVMI,WT%,WA % and RVFWT were significantly increased in MCT group,PAAT were significantly decreased in MCT group.Some rats occured tricuspid regurgitation and right ventricle occured cardiomyocyte hypertrophy in MCT group.However,no significant difference was found between Ang-(1-7) group and control group among the above parameters.Conclusion Ang-(1-7) may inhibit pulmonary arterial hypertension and right ventricular remodeling in monocrotaline-treated rats.更多还原