盐酸埃他卡林对缺氧性肺动脉高压转化生长因子β1及其受体表达的影响

Effect of iptakalim hydrochloride on the expression of TGFβ_1 and its receptor in hypoxic pulmonary hypertension

目的研究新型ATP敏感的钾通道开放剂(KATPCO)盐酸埃他卡林(IPT)对缺氧性肺动脉高压(HPH)肺组织转化生长因子β1(TGFβ1)及其受体表达的影响。方法SD大鼠随机分成IPT处理组1(对正常氧浓度饲养环境中的大鼠给予IPT1.5mg/kg灌胃)、IPT处理组2(对每日缺氧饲养的大鼠给予IPT1.5mg/kg灌胃)和正常对照组及HPH模型组(给予5ml/kg生理盐水灌胃)。测定各组大鼠肺组织TGFβ1及TGFβRⅠmRNA表达和肺血管平滑肌细胞TGFβ1及TGFβRⅠ阳性细胞数。结果HPH大鼠较正常大鼠肺组织TGFβ1转录水平mRNA的表达显著增加,而TGFβRⅠmRNA的表达减少。HPH大鼠肺血管平滑肌细胞TGFβ1蛋白质水平表达亦增加,而TGFβRⅠ阳性细胞数下降。IPT能显著抑制HPH组TGFβ1的表达。IPT显著上调HPH组TGFβRⅠ的表达。IPT处理组1与正常对照组大鼠比较,TGFβ1mRNA及TGFβ1阳性细胞数稍有下降;TGFβRⅠmRNA及TGFβRⅠ阳性细胞数稍有增加,但差异无显著性。结论HPH的增殖因素TGFβ增加。IPT可抑制HPH的这种增殖,可能的途径为TGFβ受体信号系统。

Objective To study the effects of a novel ATP sensitive potassium channel opener(K_ ATPCO) iptakalim hydrochloride(IPT) on the expression of transforming growth factor-beta 1(TGFβ1) and its receptor in hypoxic pulmonary hypertension(HPH). Methods SD rats were randomly divided into IPT treated group 1 (treated with IPT 1.5mg·kg -1·d -1 ig and exposured to normal baric condition) and 2 (IPT 1.5mg·kg -1·d -1ig and hypoxic condition),normal-controlled group and HPH-model group (treated with normal saline in a dose of 5.0ml·kg -1·d -1 ig and bred in normal baric condition and hypoxic condition respectively). mRNA expression of TGFβ_1 and transforming growth factor-beta type Ⅰ receptor(TGFβ RⅠ) were detected by reverse transcription polymerase chain reaction. TGFβ_1 and TGFβ RⅠ staining positive small pulmonary arterial smooth muscle cells(PASMC) were evaluated by S-P immunohistochemical analysis. Results TGFβ_1 mRNA expression and TGFβ_1 staining positive PASMC increased, but TGFβ RⅠ mRNA expression and TGFβ RⅠ staining positive PASMC decreased in HPH group compared with those in normal-controlled group. IPT significantly inhibited TGFβ_1 expression in HPH, as TGFβ_1 mRNA expression and TGFβ_1 staining positive PASMC decreased in IPT treated group 2. IPT remarkably up-regulated TGFβ RⅠ expression in HPH, as TGFβ RⅠ mRNA expression and TGFβ RⅠ staining positive PASMC elevated in IPT treated group 2. TGFβ1 expression elevated and TGFβ RⅠ expression reduced slightly in IPT treated group 1 compared with those in normal-controlled group.Conclusion Proliferating factors TGFβ_1 increases in HPH. IPT could inhibit the proliferation of HPH, which might be mediated through the TGFβ_1 and its receptor signal pathway.