基质金属蛋白酶-2在低氧性肺动脉高压大鼠肺血管中的表达及辛伐他汀对其影响

Expression of Matrix Metalloproteinase-2 in Pulmonary Arteries of Rats with Hypoxic Pulmonary Hypertension and Effect of Simvastatin

目的观察基质金属蛋白酶-2(MMP-2)在低氧性肺动脉高压大鼠肺血管中的表达,及辛伐他汀对其表达的调节作用。方法采用随机分组方法将30只雄性SD大鼠分为对照组、低氧组和预防组,每组10只,低氧组和预防组给予低氧处理,建立大鼠低氧性肺动脉高压模型,且预防组于低氧前给予辛伐他汀灌胃,对照组不做任何处理。3周后观察大鼠平均肺动脉压(mPAP)、右心室肥厚指数即右心室/(左心室+室间隔)和肺血管形态学指标的变化。采用免疫组织化学染色方法检测大鼠肺小动脉MMP-2表达。结果低氧组大鼠mPAP、右心室肥厚指数、肺血管形态学指标和肺小动脉MMP-2染色强度均高于对照组,差异有统计学意义(P<0.01);而预防组上述指标低于低氧组,差异有统计学意义(P<0.01)。结论 MMP-2在低氧性肺动脉高压大鼠肺血管中的表达增加,辛伐他汀可抑制其表达,预防低氧性肺动脉高压的形成。

Objective To observe the expression of matrix metalloproteinase-2（MMP-2） in hypoxic hypertension rats pneumoangiogram and the modulation of simvastatin.Methods Randomly divide 30 male SD rats were randomly divided into control group,hypoxia group and prevention group,with 10 rats in each group,hypoxia group and prevention group was given the hypoxia treatment,to establish the model of hypoxic pulmonary hypertension in rats,and the prevention group in the hypoxia of simvastatin orally,the control group without any treatment.The mean pulmonary pressure（mPAP）,right ventricular hypertrophy index-right ventricle /（left ventricle plus septum）,and the pneumoangiogram morphological index of rat were observed after three weeks.The expressing level of MMP-2 in pulmonary artererioles were measured by immunohistochemistry.Results In hypoxic group the mPAP,right ventricular hypertrophy index,and the pneumoangiogram morphological index all were higer than that in control group,the difference was statistically significant（P ＆lt; 0.01）;While in preventive group these index decreased obviously compared with that in hypoxic group,The difference was statistically significant（P ＆lt; 0.01）.Conclusion Increased expression of MMP-2 in pulmonary arteries of rats with hypoxic pulmonary hypertension,and simvastatin can prevent hypoxic pulmonary hypertension through inhibiting expression of MMP-2.