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目的研究新型ATP敏感性钾通道开放剂(KATPCO)埃他卡林(IPT)对大鼠肺组织中低氧诱导因子1α(HIF-1α)表达的影响。方法36只清洁级SD大鼠随机分成对照组、低氧性肺动脉高压(HPH)模型组和IPT处理组,每组12只。HPH模型组及IPT处理组于(10.0±0.5)%氧浓度的常压低氧舱内饲养,每天8 h,每周6 d,共4周。IPT处理组给予IPT1.5 mg.kg-1.d-1灌胃;对照组及HPH模型组给予0.9%氯化钠5 ml.kg-1.d-1灌胃。用逆转录聚合酶链反应(RT-PCR)方法检测肺组织HIF-1αmRNA表达,用Western blot方法检测肺组织HIF-1α蛋白的表达。结果HPH模型组大鼠肺动脉平均压、右室/(左室+室间隔)重量比和HIF-1αmRNA和蛋白表达均高于对照组和IPT处理组(P<0.01)。IPT处理组与对照组的HIF-1αmRNA和蛋白表达差异无统计学意义(P>0.05)。结论IPT降低肺动脉压可能与抑制HPH大鼠肺组织中的HIF-1α表达有关。
Objective To investigate the effect of a novel ATP-sensitive potassium channel opener (KATPCO) iptakalim (IPT) on the expression of hypoxia inducible factor 1α (HIF-1α) in the lung tissue of rats. Methods Thirty-six clean-grade SD rats were randomly divided into control group, hypoxic pulmonary hypertension (HPH) model group and IPT-treated group, 12 rats in each group. The HPH model group and the IPT treatment group were housed in a normal pressure hypoxic chamber of (10.0 ± 0.5)% oxygen concentration for 8 hours a day for 6 days a week for 4 weeks. IPT treatment group given IPT1.5 mg.kg-1.d-1 gavage; control group and HPH model group given 0.9% sodium chloride 5 ml.kg-1.d-1 gavage. The expression of HIF-1αmRNA in lung tissue was detected by reverse transcription-polymerase chain reaction (RT-PCR). The expression of HIF-1α protein in lung tissue was detected by Western blot. Results Compared with the control group and the IPT group, the mean pulmonary arterial pressure, right ventricular / (left ventricular + septal) weight ratio and the expression of HIF-1αmRNA and protein in HPH model group were significantly increased (P <0.01). There were no significant differences in HIF-1αmRNA and protein expression between IPT group and control group (P> 0.05). Conclusion IPT decreased pulmonary arterial pressure may be related to the inhibition of HIF-1α expression in the lung tissue of HPH rats.