三七皂苷在jnk介导的低氧高二氧化碳性肺动脉高压模型中的机制探讨.docVIP

三七皂苷在JNK介导的低氧高二氧化碳性肺动脉高压模型中的机制探讨 　　[摘要] 目的 研究JNK信号通路在大鼠低氧高二氧化碳性肺动脉高压（HHPH）发生发展中的动态变化，探讨三七皂苷（PNS）防治HHPH的机制。 方法 复制慢性HHPH的SD大鼠模型，分为正常组（N，n=10），低O2高CO2组（H4w，n=10）及PNS治疗组（Hp4w，n=10）。RT-qPCR及Western blot检测JNK mRNA及蛋白表达情况。原代培养SD大鼠肺动脉平滑肌细胞（PASMCs），取2～5代对数生长期细胞，分为正常组（N）、低O2高CO2组（H）及PNS治疗组（R10、R50、R100），PNS治疗组分别用不同浓度（10、50、100 mg/L）的三七皂苷单体R1进行处理，24 h后收集细胞，RT-qPCR及WesternBlot检测JNK mRNA及蛋白表达情况。然后用R1及JNK抑制剂SP600125分别及联合处理PASMCs 5 d，CCK8检测细胞增殖情况。 结果 ①与N组相比，H4w组和Hp4w组mPAP均明显增高（P 　　[关键词] 三七皂苷；低氧高二氧化碳；肺动脉高压 　　[中图分类号] R543.2 [文献标识码] A [文章编号] 1673-7210（2017）06（c）-0007-05 　　[Abstract] Objective To investigate the dynamic change of JNK signaling pathway in the occurrence and development of hypoxic hypercapnia pulmonary hypertension in rats， discuss the mechanism of panax notoginoside （PNS） in the protection of hypoxic hypercapnia pulmonary hypertension. Methods Rats pathological models of hypoxic hypercapnia pulmonary hypertension were established： SD rats were randomly divided into three groups （n=10）： normal group （N group）， hypoxic hypercapnia for 4 week group （H4w group）， and PNS-injected group （Hp4w group）. RT-qPCR and Western blot were used to detect the expression of JNK. Primary cultured PASMCs， isolated from SD rats， were incubated in logarithmic growth phase from the 2nd to 5th generation. PASMCs were divided into five groups： normal group （N group）， hypoxic hypercapnia group （H group）， and R1 treated group with different concentrations （10， 50 and 100 mg/L） of notoginsenoside monomer R1 under the condition of 6% CO2 plus 1% O2 for 24 h （R10， R50 and R100 groups）. The expressions of JNK mRNA and protein levels were detected by RT-qPCR and Western blot. PASMCs were treated with R1 and JNK inhibitor SP600125 for 5 days， CCK8 was used to detect the proliferation of PASMCs. Results ①The mPAP in H4w and Hp4w group was higher than that of N group （P 　　[Key words] Panax notoginoside； Hypoxic hypercapnia； Pulmonary arterial hypertension 　　低氧高二氧化碳性肺动脉高压（hypoxic hypercapnia pulm