三七总皂苷对低氧大鼠肺动脉压和肺组织p38 MAPK表达的影响

Effect of Panax notoginoside on pulmonary arterial pressure and expression of p38 MAPK in lung tissues of hypoxic rats

目的:探讨三七总皂苷(PNS)对低氧大鼠p38丝裂原活化蛋白激酶(p38 MAPK)表达的影响,及预防低氧性肺动脉高压(HPH)的作用和机制。方法:将30只SD大鼠随机分为3组:正常对照组、低氧组和低氧+PNS组。观察各组大鼠平均肺动脉压(mPAP)、平均颈动脉压(mCAP)和右心室/(左心室+室间隔重量)比[RV/(LV+S)],免疫组化法和RT-PCR法分别检测肺小血管壁磷酸化p38 MAPK(p-p38 MAPK)蛋白和肺组织中mRNA的含量。结果:与对照组相比,低氧组大鼠mPAP、RV/(LV+S)明显升高,肺小动脉p-p38 MAPK及肺组织p38 MAPK mRNA含量显著升高(P<0.05)。低氧+PNS组mPAP、RV/(LV+S)、肺小动脉p-p38 MAPK及肺组织p38 MAPK mRNA含量明显低于低氧组(P<0.05)。结论:PNS具有显著预防HPH的作用,其机制可能与其降低p38 MAPK mRNA的表达有关。

AIM：To observe the effect of Panax notoginoside（PNS） on the pulmonary artery pressure and the p38 mitogen-activated protein kinase（p38 MAPK） in lung tissues of rats treated with hypoxia.METHODS： Thirty adult male SD rats were randomly divided into 3 groups.The rats in normal control group were exposed to normal conditions,the rats in hypoxia group were exposed to isobaric hypoxia,and the rats in hypoxia＋PNS group were treated with PNS under the condition of hypoxia.After 4 weeks of treatment,the mean pulmonary arterial pressure（mPAP） and the mean carotid arterial pressure（mCAP） were measured by cardiac catheterization.The heart was isolated,and the right ventricle（RV）,left ventricle plus ventricular septum（LV＋S） were weighed to calculate the ratio of RV/（LV＋S）.The quantity of phospho-p38 MAPK（p-p38 MAPK） in rat pulmonary arterioles was determined by the method of immunohistochemistry and the mRNA content of p38 MAPK was tested by RT-PCR.RESULTS： The mPAP and RV/（LV＋S） in hypoxia group were higher than those in normal control group.The expression of p-p38 MAPK in rat pulmonary arterioles and p38 MAPK mRNA in the lung tissues were higher than those in normal control group（P0.05）.The mPAP,RV/（LV＋S）,the expression of p-p38 MAPK in rat pulmonary arterioles and p38 MAPK mRNA in the lung tissues in hypoxia＋PNS group were significantly lower than those in hypoxia group（P0.05）.CONCLUSION： PNS possesses the preventive and therapeutic effect on hypoxic pulmonary hypertension by decreasing p-p38 MAPK and down-regulation of p38 MAPK mRNA in the lungs.