Iptakalim, a novel ATP-sensitive potassium channel opener, inhibits pulmonary arterial smooth muscle cell proliferation by downregulation of PKC-α

Iptakalim is a new ATP-sensitive potassium （KATp） channel opener, and it inhibits the proliferation of pulmonary arterial smooth muscle cells （PASMCs） and pulmonary vascular remodeling. However, the underlying mechanism remains unclear. In the present study, we found that iptakalim significantly decreased pulmonary artery pressure, inhibited pulmonary ariery remodeling and PKC-α overexpression in chronic hypoxia in a rat pulmonary hypertension model. Iptakalim reduced hypoxia-induced expression of PKC-α, and abolished the effect of hypoxia on PASMC proliferation significantly in a dose-dependent manner in vitro. Moreover, these effects were abol- ished by glibenclamide, a selective KArp channel antagonist. These results indicate that iptakalim inhibits PASMC proliferation and pulmonary vascular remodeling induced by hypoxia through downregulating the expression of PKC-α. Iptakalim can serve as a novel promising treatment for hypoxic pulmonary hypertension.

滨蒿内酯对大鼠哮喘模型气道平滑肌增殖及PKC-α蛋白表达的影响

目的观察滨蒿内酯对哮喘大鼠气道壁平滑肌增殖及PKC-α(protein kinase C-α,蛋白激酶C-α)表达的影响,探讨滨蒿内酯治疗哮喘的作用机制。方法40只雄性大鼠随机分成4组:正常对照组(N组)、哮喘组(A组)、地塞米松治疗组(D组)及滨蒿内酯治疗组(S组),以卵清蛋白致敏和激发方法建立哮喘大鼠动物模型并给予相应治疗。测定各组肺功能,检测支气管肺泡灌洗液(BALF)中白细胞总数及嗜酸粒细胞(EOS)计数;用免疫组化法检测PKC-α蛋白表达水平、光镜下测定平滑肌层厚度及内外径。结果大鼠致敏2周及诱发哮喘4周后,肺功能测定表现为呼气时间延长,呼气峰压明显增大;A组BALF中的白细胞总数及Eos计数均较N组明显升高。哮喘模型组气道壁PKC-α蛋白含量和平滑肌层厚度较正常组均显著增加(均为P<0.001),气道内外径比值较正常组减小(P<0.001)。气道壁平滑肌层厚度与PKC-α蛋白表达呈正相关(rs=0.771,P<0.01)。结论滨蒿内酯能减轻哮喘大鼠气道壁平滑肌层的增厚并抑制PKC-α的表达。