冬凌草甲素对肺动脉高压大鼠肺动脉压的调控作用及机制研究

目的:探讨冬凌草甲素对低氧高二氧化碳肺动脉高压大鼠肺动脉压的调控作用及机制研究。方法:清洁SD大鼠随机分为3组,正常对照组、低氧高二氧化碳组、低氧高二氧化碳加冬凌草甲素组。低氧高二氧化碳时间为4周。测定各组的平均肺动脉压(mPAP)、右心室重量比[LV/(RV S)]、管壁面积/管总面积(WA%)、管壁厚度/血管外径(WT%)、门冬氨酸特异半胱氨酸蛋白酶(caspase)3及9的活力、细胞色素C(Cyt-c)的表达。并用透射电镜观察其超微结构变化。结果:低氧高二氧化碳组mPAP、LV/(RV S)、WA%、WT%均高于正常对照组(P<0.01),caspase3、9活性,Cyt-c表达均低于正常对照组(P<0.01);冬凌草甲素干预组mPAP、LV/(RV S)、WA%、WT%均低于低氧高二氧化碳组(P<0.01),caspase3、9活性,Cyt-c高于低氧高二氧化碳组(P<0.01)。冬凌草甲素组可以发现肺小动脉平滑肌细胞核固缩,核膜间隙增大,线粒体浓聚,部分线粒体肿胀。结论:冬凌草甲素可以有效降低肺动脉压。其机制可能系通过诱导肺动脉平滑肌细胞线粒体途径凋亡,从而抑制肺动脉重构。

Study of the Regulation Effects of Oridonin on Pulmonary Artery Pressurein Pulmonary Hypertension Rats with Chronic Hypoxia-hypercapnia and Its Mechanism

Objective:To study the regulation effects of Oridonin on pulmonary artery pressure in pulmonary hypertension rats with hypoxia-hypercapnia and its mechanism.Methods:SD rats were divided into three groups randomly:the normal control group(NC),the hypoxia-hpercapniagroup(HH),and the hypoxia-hpercapnia plus Oridonin group(O).The time of hypoxia-hypercapnia was 4 weeks.The mean pulmonary artery pressure(mPAP),right ventricular rate(RV/(LV S)),percentage of thickness of pulmonary artery wall in vascular external diameter(WT%),percentage of pulmonary artery wall area in total vascular area(WA%),vitality of caspase3 and caspase9,expression cyt-c of each group were observed.The ultrastructural organization was observed through transmission electron microscopy.Results:The mPAP,RV/(LV S),WT%,WA% in group HH were significantly higher than those in group NC(P<0.01),and those in group O were lower than that in group HH(P<0.01);the vitality of caspase3 and caspase9,expression of cyt-c in group HH were lower than those in group NC,but those in group O were higher than that in group HH.The lung arterial smooth muscle cells are pycnosis,nuclear membrane spaces are enlargement,some mitochondrias are diminution,somes are swelling.Conclusion:Oridonin can lower pulmonary pressure effectively.It may induce smooth cell apoptosis through mitochondrial dependent pathway in pulmonary artery hypertension rats,suppress pulmonary artery structural remodeling.