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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。
Objective: To investigate the regulation and mechanism of oridonin on pulmonary arterial pressure in rats with hypoxic hypercapnic pulmonary hypertension. METHODS: Clean SD rats were randomly divided into 3 groups: normal control group, hypoxic hypercapnia group, hypoxia hypercapnia, and oridonin group. The hypoxia and hypercapnia time is 4 weeks. Mean pulmonary artery pressure (mPAP), right ventricular weight ratio [LV/(RV+S)], wall area/tube total area (WA%), wall thickness/vessel outside diameter (WT%), gates were determined for each group. Activity of caspase 3 and 9 and cytochrome C (Cyt-c) expression. The transmission electron microscope was used to observe the ultrastructural changes. Results: mPAP, LV/(RV+S), WA%, and WT% in the hypoxic hypercapnia group were higher than those in the normal control group (P<0.01). The caspase 3 and 9 activity and Cyt-c expression were lower in the hypoxia and hypercapnia group than in the normal control group ( P<0.01); mPAP, LV/(RV+S), WA%, WT% were lower in oridonin treatment group than in hypoxia hypercapnia group (P<0.01), caspase 3, 9 activity, Cyt-c high In hypoxia and hypercapnia group (P <0.01). Oridonin group can find the pyknosis of smooth muscle cells of pulmonary arterioles, the increase of nuclear membrane space, the accumulation of mitochondria, and swelling of some mitochondria. Conclusion: Oridonin can effectively reduce pulmonary artery pressure. The mechanism may be to induce pulmonary arterial remodeling by inducing apoptosis in the mitochondrial pathway of pulmonary artery smooth muscle cells.