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首页> 中文期刊> 《中国病理生理杂志》 >三七皂苷单体R1抑制低氧高二氧化碳诱导的肺动脉平滑肌细胞p38MAPK信号通路的活化

三七皂苷单体R1抑制低氧高二氧化碳诱导的肺动脉平滑肌细胞p38MAPK信号通路的活化

         
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目的:探讨三七皂苷单体R1(R1)减轻低氧高二氧化碳(CO2)性肺动脉收缩的作用及其与p38 MAPK信号通路的关系.方法:原代培养雄性SD大鼠肺动脉平滑肌细胞(PASMCs),取第2至5代对数生长期细胞至低氧高CO2(1% O2,6% CO2)条件下继续培养,并分别用8、40、100 mg/L R1 孵育24 h后收集细胞,采用免疫印迹法测定p38 MAPK磷酸化蛋白表达,半定量RT-PCR检测p38 MAPK mRNA的表达.结果:Western blotting和RT-PCR结果显示,低氧高CO2组p-p38 MAPK蛋白和p38 MAPK mRNA表达明显高于对照组(N)组(P＜0.01).与低氧高CO2组相比,R1(8、40、100 mg/L)不同程度抑制了p-p38 MAPK蛋白和p38 MAPK mRNA的表达(P＜0.01),并呈剂量依赖关系.结论:低氧高CO2诱导PASMCs p38 MAPK活化,三七皂苷单体R1可能通过抑制p38 MAPK通路减轻低氧高CO2性肺动脉收缩.%AIM:To explore the mechanism of notoginsenoside monomer R1 ( R1 ) against hypoxic hypercapnia - induced pulmonary vasoconstriction ( HHPV ) by investigating the effect of R1 on p38 mitogen - activated protein kinase ( p38MAPK ) signaling pathway in pulmonary arterial smooth muscle cells ( PASMCs ) under the condition of hypoxia and hypercapnia. METHODS: Primary cultured PASMCs, which were isolated from Sprague - Dawley rats, were incubated in logarithmic growth phase from the 2nd to 5th generation with different concentrations ( 8, 40 and 100 mg/L ) of R1 under the condition of 6% CO2 plus 1% O2 for 24 h. The expression of p38 at mRNA and protein levels was detected by RT - PCR and Western blotting,respectively. RESULTS: The results of Western blotting and RT - PCR analysis indicated that the protein and mRNA expression levels of p - p38 MAPK were significantly higher in hypoxic hypercapnia group with DM-SO control than those in normoxia control group ( P <0. 01 ). In R1 treatment groups, the levels of p - p38 MAPK protein and p38 MAPK mRNA were markedly decreased ( P < 0. 01 ) in a dose - dependent manner. CONCLUSION: p38 MAPK signaling pathway may mediate hypoxic hypercapnia pulmonary vasoconstriction in rats. Notoginsenoside monomer R1attenuates HHPV, which may be related to blockage of p38 MAPK signal pathway.

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