低氧性肺动脉高压雄性大鼠肺组织中的p38 MAPK/NF-κB信号通路相关蛋白的表达

The protein expression of p38 MAPK/NF-kB pathway in lung tissue of male rats with hypoxic pulmonary hypertension

目的构建低氧性肺动脉高压(hypoxic pulmonary hypertension,HPH)雄性大鼠模型,了解低氧性肺动脉高压雄性大鼠肺组织中的p38 MAPK/NF-κB信号通路相关蛋白的表达特点。方法将16只SPF级雄性SD大鼠随机分为control组、hypoxic组,每组8只。将hypoxic组大鼠置低压低氧舱(模拟海拔5000 m)饲养、control组置舱外饲养(海拔2260 m),持续28 d。使用右心导管术检测大鼠平均肺动脉压(mean pulmonary arterial pressure,mPAP),分离心脏并称重以计算RVHI;用HE染色法观察肺小动脉病理形态学变化,计算血管壁面积占血管总面积的百分比(WA%)、血管壁厚度占血管直径的百分比(WT%);用Western Blotting法检测肺组织p38、p-p38、IκBα、p-IκBα、p65、p-p65蛋白的表达水平。结果同control组比较,hypoxic组大鼠mPAP、RVHI升高(P<0.05),大鼠肺小动脉管壁明显增厚,管腔变窄,WA%、WT%升高(P<0.05);hypoxic组大鼠肺组织p-p38、p-IκBα、p-p65蛋白的表达水平均升高(P<0.05),p-p38/p38、p-IκBα/IκBα、p-p65/p65同样升高(P<0.05)。结论在低氧条件下,HPH雄性大鼠肺组织中的p-p38、p-IκBα、p-p65蛋白表达水平均升高,p38 MAPK/NF-κB信号通路被激活。

Objective To investigate the protein expression of p38 MAPK/NF-kB pathway in lung tissue of male rats'model with hypoxic pulmonary hypertension.Methods Sixteen Specific pathogen Free(SPF)male SpragueDawley(SD)rats were randomly divided into control group and hypoxic group,with 8 rats in each group.Rats in the hypoxic group were placed in a low-pressure oxygen Chamber(simulated altitude 5000 m),while rats in control group were exposed to room air(altitude 2260 m)for 28 days.The mean pulmonary artery pressure(mPAP)was measured using Right heart catheterization,the heart of rats was separated and weighed to calculate the RVHI;the percentage of vessel wall area to total vessel area(WA%)and the percentage of vessel wall thickness to vascular diameter(WT%)were calculated using HE stains evaluate pathological changes of pulmonary arterioles;The expression levels of p38,p-p38,IkBα,p-IkBα,p65 and p-p65 proteins in lung tissue were detected using western blotting.Results Compared with the control group,the mPAP and RVHI of hypoxic rats were higher(P<0.05),the pulmonary arteriole wall of hypoxic rats was obviously thickened,the lumen was narrowed,WA%and WT%were increased(P<0.05);The protein expression levels of p-p38,p-lkBαand p-p65 in the lung tissue of rats in the hypoxiac group were all increased(P<0.05),and p-p38/p38,p-IkBα/IkBαand p65/p-p65 were also increased(P<0.05).Conclusion Under hypoxic condition,the expression levels of p-p38,p-IkBαand p-p65 protein in lung tissue of HPH male rats were all increased,and p38 MAPK/NF-kB signal pathway was activated.