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

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.