辛伐他汀抑制肺动脉高压大鼠肺动脉内COX-2的表达

Effect of simvastatin on expression of cyclooxygenase-2 in a rat model of pulmonary artery hypertension

目的:探讨3-羟基-3-甲基戊二酰辅酶A还原酶(HMG-COA)抑制剂辛伐他汀对肺动脉高压(PAH)大鼠环氧合酶(COX-2)的影响。方法:雄性SD大鼠30只,随机分为正常对照组、PAH模型组和辛伐他汀干预组,每组10只。用PM-8000型多参数监护仪及Elastin Van Gieson染色法,分别测定各组大鼠的平均肺动脉压力及肺小动脉新生内膜增殖度和平均血管阻塞计分(VOS)的改变。用免疫组化染色法和荧光定量PCR法,测定肺组织中的COX-2在蛋白和基因的水平上表达的差异。结果:PAH模型组大鼠的平均肺动脉压力、肺小动脉新生内膜增殖度和VOS的改变,均较正常对照组显著增加(P<0.05),其COX-2在蛋白和基因的水平上的表达都明显高于正常对照组(P<0.05)。辛伐他汀干预后,大鼠的平均肺动脉压力、肺小动脉新生内膜增殖度和VOS,均较PAH模型组显著减少(P<0.05),COX-2在蛋白和基因的水平上的表达都明显低于PAH模型组(P<0.05)。结论:辛伐他汀可抑制肺动脉内COX-2的表达来抑制PAH形成。

AIM： To explore the effect of simvastatin, an inhibitor of HMG-COA, on the expression of cyclooxygenase-2 （COX-2） in a rat model of pulmonary artery hypertension （PAH）. METHODS： Thirty male Sprague Dawley rats were randomized into three groups equally： control group, PAH model group and treatment group with intervention of simvastatin. Changes of mean pulmonary arterial pressure （mPAP）, endomembrane proliferation in the pneumono-arteriole and the average vascular occlusion scores （VOS） were measured. Gene and protein expression of COX-2 were also measured, respectively, by fluorescent quantitation PCR and immunohistochemistry. RESULTS： mPAP, pneumono-arteriole and VOS increased significantly in the PAH model group compared with those in the control group （P 〈 0.05 ）. Expression of COX-2 both at the level of gene and protein was significantly higher in the PAH model group than in the control group （P 〈 0.05）. With the intervention of simvastatin, mPAP and endomembrane proliferation in the pneumono-arteriole and VOS decreased dramatically （P 〈 0. 05 ） compared with those in the model group （P 〈 0.05）. CONCLUSION： PAH model has been induced successfully by pneumonoresection ＋ monocrotaline （MCT） and simvastatin may hamper PAH partly by inhibiting the expression of COX-2 in pulmonary artery.