论文部分内容阅读
The voltage-gated K+ (Kv) channels play an essential role in the etiology of chronic hypoxic pulmonary arterial hypertension (CH-PAH).Tanshinone ⅡA (TⅡA), a major active component of Salvia miltiorrhiza Bunge (S.miltiorrhiza), has many biological protective effects.In the present study, we investigated whether Kv channels were responsible for the protective effect of TⅡA on CH-PAH.In acute hypoxia experiments, the effects of TⅡA (10-5 M) or 4-aminopyridine (4-AP, lmM) on intrapulmonary artery (IPA) rings isolated from healthy rats were measured.And then the IKV currents of pulmonary artery smooth muscle cells (PASMCs) isolated from healthy rats were determined in the absence or presence of TⅡA (5ug/ml or 25ug/ml) or 4-AP (1mM).In chronic hypoxia experiments, rats were challenged by intermittent hypoxia exposure for 4 weeks with or without TⅡA (10 mg/kg) treatment.Subsequently, the hemodynamic data and the pathomorphological changes of pulmonary arteries were gathered.Kv2.1 and Kv1.5 in pulmonary arteries were tested by Westem blotting and RT-PCR, respectively.PASMCs were detached from chronic hypoxia exposure rats to evaluate the IKV currents.Results showed that TⅡA markedly attenuated acute hypoxia-induced IPA rings vasoconstriction and recovered the down-regulation of IKV currents in PASMCs.Besides, TⅡA significantly restrained chronic hypoxia-induced the right ventricular systolic pressures (RVSP) and right ventricle (RV) hypertrophy, inhibited pulmonary artery wall remodeling, accompanied with modulating the expression of Kv2.1 and Kvl.5, and reversing the down-regulation of IK V currents.TⅡA is thus an attractive potential therapy for CH-PAH.