Ang-(1-7)与肺高压状态下肺血管平滑肌细胞的增生

背景：Ang-(1-7)虽然具有抗血管平滑肌细胞增殖作用，但在不同的血管床中其作用可能存在差异。直接给予外源性Ang-(1-7)是否可抑制肺动脉高压大鼠肺血管平滑肌细胞的增殖尚不清楚。 目的：探讨Ang-(1-7)对野百合碱诱导的肺动脉高压大鼠肺血管平滑肌细胞增殖的影响。 方法：雄性SD大鼠颈部一次性注射60 mg/kg野百合碱制备肺动脉高压模型。24 h后，分别经微泵持续泵入Ang-(1-7)(治疗组)或生理盐水(模型组)，并设立未造模的对照组。给药2，4周，测定大鼠的右心室收缩压、心室质量、肺小动脉管壁厚度占管径的百分比及管壁面积占血管总面积的百分比。免疫组织化学方法检测肺血管平滑肌细胞α-平滑肌肌动蛋白及增殖细胞核抗原的表达。 结果与结论：野百合碱诱导2周，与对照组比较，模型组大鼠右心室收缩压、各心室的质量无明显变化，肺小动脉管壁厚度占管径的百分比、管壁面积占血管总面积的百分比、增殖细胞核抗原阳性率显著增高，α-平滑肌肌动蛋白显著降低；野百合碱诱导4周，模型组大鼠右心室收缩压、各心室的质量、肺小动脉管壁厚度占管径的百分比、管壁面积占血管总面积的百分比、增殖细胞核抗原阳性率均显著增高，α-平滑肌肌动蛋白显著降低。而治疗组上述指标与对照组比较差异无显著性意义   (P > 0.05)。说明在野百合碱诱导的肺动脉高压模型中，在肺动脉压增高之前已有肺血管形态学的变化，Ang-(1-7)可通过减轻肺血管平滑肌细胞的增生抑制大鼠肺动脉压的升高。

Effects of Ang-(1-7) on hyperplasia of pulmonary vascular smooth muscle cells in pulmonary arterial hypertension rats

BACKGROUND:Ang-(1-7) is considered one of the biologically active products of renin-angiotensin system. Ang-(1-7) might inhibit the vascular smooth muscle cells. However, effects of Ang-(1-7) in different vascular beds are different. Effects of Ang-(1-7) on the model of pulmonary artery hypertension induced by monocrotaline (MTC) are unknown. OBJECTIVE:To investigate the therapeutic effect of Ang-(1-7) on proliferation of the pulmonary vascular smooth muscle cells in rat model of pulmonary arterial hypertension. METHODS:Adult SD rats were randomly divided into three groups: control group, MCT group and MCT+Ang-(1-7) group. Rats in MCT group and MCT+ Ang-(1-7) group received 60 mg/kg MCT injection subcutaneously and after 24 hours received either saline or 24 ug/kg/h of Ang-(1-7) injection via osmotic minipumps for 2 and 4 weeks. These rats in control group were firstly injected saline subcutaneously and then received saline injection via osmotic minipumps for two and four weeks. Right ventricular systolic pressure (RVSP) was measured. The animals’ hearts were measured to calculate the ratio of right ventricle to left ventricle plus septum (RV/LV+S), right ventricle mass to body weight (RV/BW) and left ventricle plus septum mass to body weight (LV+S/BW). Percentage of wall thickness (WT%) and percentage of wall area (WA%) of pulmonary arterioles were evaluated. Immunohistochemical stains were used to identifyα-actin and proliferation cells nuclear antibody (PCNA) distribution in pulmonary arteries. RESULTS AND CONCLUSION:At 2 weeks after injection, no significant difference was found between MCT and control group in RVSP and RVHI. Compared with control group, WT%, WA% and the positive ratio of PCNA were significantly increased and α-actin was significantly decreased in MCT group. At 4 weeks after injection, compared with control group, RVSP, RVHI, WT%, WA % and the positive ratio of PCNA were significantly increased and α-actin was significantly decreased in MCT group. However, no significant difference was found between MCT+Ang-(1-7) group and control group among the above parameters (P > 0.05). MCT-induced pulmonary arteriolar remodeling is prior to the increase of pulmonary arterial pressure in rats. Ang-(1-7) might inhibit the vascular smooth muscle cells in rat model of pulmonary arterial hypertension.