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目的:探讨低氧性肺动脉高压(HPH)大鼠肺小动脉Siah1的动态表达变化及作用。方法:40只成年雄性Wistar大鼠随机分为对照组和低氧3d、7d、14d、21d组,每组8只,常压间断低氧复制HPH大鼠模型。测各组大鼠平均肺动脉压(mPAP)、右心室肥大指数(RVHI)、血管形态学指标;原位杂交、RT-PCR检测肺内Siah1mRNA表达,免疫组化、Westernblot检测其蛋白质水平。结果:①低氧7d后,肺小动脉出现血管重塑,且mPAP明显上升;低氧14d后,肺小动脉重塑更明显,mPAP达高峰。RVHI在低氧14d后明显增加。②Siah1mRNA在对照组肺小动脉壁呈弱阳性表达,低氧7d后显著增高,低氧14d后达高峰,低氧21d后下降但仍高于对照组。免疫组化显示,Siah1蛋白在对照组肺小动脉壁呈弱阳性表达,低氧7d后显著增高,低氧14d后达高峰,低氧21d后下降但仍高于对照组。③大鼠肺小动脉壁Siah1蛋白与Siah1mRNA呈正相关;Siah1mRNA、Siah1蛋白与mPAP、重塑指数、RVHI均呈正相关。结论:慢性低氧诱导肺小动脉壁Siah1表达增加,进而在HPH发病过程中发挥一定的作用。
Objective: To investigate the dynamic changes of Siah1 in pulmonary arterioles in hypoxic pulmonary hypertension (HPH) rats. Methods: Forty adult male Wistar rats were randomly divided into control group and hypoxia for 3 days, 7 days, 14 days and 21 days. Eight rats in each group were randomly divided into hypoxia and HPH rats. The mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RVHI) and morphological changes of blood vessels in each group were measured. The expression of Siah1 mRNA was detected by in situ hybridization and RT-PCR. The protein level was detected by immunohistochemistry and Western blot. RESULTS: ① After hypoxia for 7 days, pulmonary arterioles developed remodeling and mPAP increased significantly. After 14 days of hypoxia, remodeling of pulmonary arterioles was more obvious and mPAP peaked. RVHI significantly increased after 14 days of hypoxia. ②Siah1mRNA expression was weakly positive in pulmonary arterioles in control group, increased significantly after hypoxia for 7 days, peaked 14 days after hypoxia, but decreased after 21 days of hypoxia, but still higher than that of control group. Immunohistochemistry showed that Siah1 protein was weakly positive in the pulmonary arterioles of the control group, significantly increased after hypoxia for 7 days, peaked 14 days after hypoxia, and decreased after 21 days of hypoxia, but still higher than that of the control group. ③ The Siah1 protein in rat pulmonary arterioles was positively correlated with Siah1mRNA; Siah1mRNA and Siah1 protein were positively correlated with mPAP, remodeling index and RVHI. Conclusion: Chronic hypoxia induced the expression of Siah1 in pulmonary arterioles, which may play a role in the pathogenesis of HPH.