p38-MAPK信号通路在HHPH中的作用及三七总皂苷干预

Role of P38-MAPK signal transduction pathway and effect of panax notogino side in rats with hypoxic hypercapnia pulmonary hypertension

目的:研究p38-MAPK信号通路在大鼠低O2高CO2性肺动脉高压(HHPH)发生发展中的动态变化;探讨三七总皂苷(PNS)防治低O2高CO2性肺动脉高压的机制。方法:复制慢性HHPH大鼠模型,分为正常组(N),低O2高CO23 d组(H3d)、1周组(H1w)、2周组(H2w)、4周组(H4w),及PNS治疗组(Hp),Hp组腹腔注射血塞通注射液(成分为PNS和生理盐水)。Western印迹法、免疫组织化学技术检测肺组织及肺血管P-p38、p38蛋白的表达。结果:①H1w、H2w、H4w和Hp组的WA/TA均高于N组(P均<0.05),但H3d组较N组增加不明显(P>0.05),Hp组WA/TA明显低于H4w组(P<0.05)。②肺组织P-p38蛋白在N组表达不明显,在H3d、H1w、H2w、H4w组均有高水平表达。③肺小动脉壁P-p38蛋白在N组和H3d组表达呈阴性或弱阳性,在H1w、H2w、H4w组有高水平表达,较N组差异有统计学意义(P<0.05)。④Hp组肺组织P-p38,肺小动脉壁P-p38蛋白表达较低O2高CO2组降低(P<0.05)。结论:p38-MAPK信号通路介导了大鼠HHPH的形成。PNS可减轻这一过程,其机制可能和PNS抑制P-p38表达有关。

Objective： To investigate the role and significance of P38-MAPK in the pathological process of hypoxic hypercapnia pulmonary hypertension in rats,and the protection of panax notogino side（PNS）.Methods： ①To set up rat pathological model of hypoxic hypercapnia pulmonary hypertension： seventy two male SD rats（200~280 g） were randomly divided into six groups（n=12）,which were normal group（N group）,hypoxic hypercapnia for 3-day group（H3d）,hypoxic hypercapnia for 1-week group（H1w）,hypoxic hypercapnia for 2-week group（H2w）,hypoxic hypercapnia for 4-week group（H4w） and PNS-injected group（Hp）.The rats of PNS-injected group were injected PNS before being placed in the chamber（50 mg/（kg·d）,ip）,and other groups were injected normal sodium（2 ml/kg,ip）.②The shapes of pulmonary artery were detected by HE staining.③Western blot was used to study the protein expression of p38-MAPK.④The expression of p38-MAPK in lung tissue and pulmonary blood vessel was investigated by immunohistochemistry.Results： ①The ratio of vessel wall area/total area（WA/TA） in H1w,H2w,H4w and Hp group was higher than that of N group（P 0.05）,but that of H3d group did not change obviously（P 0.05 vs N group）.The ratio of WA/TA in Hp group was obviously lower than that of H4w group（P 0.05）.②The levels of P-p38 protein was markedly ascended in H3d group（0.225±0.071） compared with N group（0.012±0.006）,and expression of P-p38 protein was significantly positive in H1w、H2w、H4w groups.（P0.05）.③As P-p38 protein in pulmonary arterial tunica intima and tunica media,sterile expression in N group（0.099±0.015）and H3d group（0.107±0.013） contrasted to H4w group（0.124±0.025,P0.05）,then tended to rise in H2w、H4w group（P0.05）.④In pulmonary tissue,the levels of P-p38 protein in PNS-injected group were lower 53.02%（P0.05） than those in H4w group.In pulmonary arterial tunica intima and tunica media the levels of P-p38 protein in PNS-injected group were lower 87.33%（P0.05） than those in H4w group.Conclusion： p38-MAPK as a signal transduction may play an important role in the development of hypoxia induced pulmonary hypertension.The effect of PNS on reducing pulmonary hypertension and improving pulmonary vascular wall remodeling may be related to its inhibiting expression of p38 MAPK.