辛伐他汀对野百合碱诱导肺动脉高压大鼠肺组织中NF-κB表达及血清C反应蛋白和TNF-α水平的影响

Effects of Simvastatin on the expression of NF-kB in lung and the serum levels of CRP and TNF-α in rats with pulmonary hypertension induced by Monocrotaline

目的观察辛伐他汀对野百合碱(MCT)诱导的肺动脉高压大鼠核因子NF-κB的表达及血清C反应蛋白和TNF-α水平的影响,探讨辛伐他汀治疗肺动脉高压的作用机制。方法将30只健康雄性SD大鼠随机分为正常对照组,MCT诱导的肺动脉高压组(模型对照组),辛伐他汀干预治疗组(治疗组)。注射野百合碱建立动物模型,右心导管法检测大鼠平均肺动脉压(mPAP),测量右心室肥大指数(RVHI)。采用Western blot法检测各组大鼠IKKα,IκBα和NF-κB p65蛋白表达情况。结果治疗组大鼠的mPAP和RVHI均显著低于模型对照组;治疗组大鼠肺组织NF-κB p65蛋白表达及血清C反应蛋白和TNF-α水平均明显低于模型对照组,差异均有统计学意义(P<0.01或0.05)。结论辛伐他汀可有效降低MCT诱导肺动脉高压模型大鼠的肺动脉压、改善肺血管重构,其机理可能与抑制肺组织核因子NF-κB的表达及炎症因子的释放有关。

Objective To observe the effects of simvastatin on the expression of nuclear factor-kappaB （NF-xB） in lung and the serum levels of C reactive protein （CRP） and tumor necrosis factor-α（TNF-α） in rats with pulmonary hypertension induced by monoerotaline （MCT）. Methods Thirty male SD rats were randomly and equally divided into three groups, the control group, MCT-induced pulmonary hypertension group （model group） and treated group with simvastatin （S group）. Pulmonary hypertension in rats was induced by injection with MCT. The mean pulmonary arterial pressure （mPAP） was measured with the right ventricular duct method and the right ventricular hypertrophy index （RVHI） was measured. the index of wall thickness of pulmonary arteriole was measured by a computerized image analyzer. The expression of IKKα, IkBα, NF-kB and P65 in lung was detected by western blot. the serum levels of CRP and TNF-α were measured by ELISA. Results： mPAP and RVHI in the model group were significantly higher than those in the control group and the S group, with no significant difference in between the control group and the S group. The expression of NF-kB and 65 and the serum levels of CRP and TNF-α in the S group were significantly lower than those in the model group. The expression of IxBαin the S group was higher than that in the model group. Conclusion： Simvastatin has a therapeutic effect on rat pulmonary hypertension induced by MCT through down-regulatlon of NF-kB expression and inhibition of the production of CRP and TNF-α.