Siah2负调控脯氨酰羟化酶3表达在大鼠低氧性肺动脉高压中的意义  

Down-regulation of prolyl hydroxylases 3 by Siah2 in rats with hypoxia-induced pulmonary hypertension

作　　者：潘坤[1] 戴爱国 张泽明[1] 陈云荣 尹文斌[1] 杜宇[1] 

机构地区：[1]河北大学附属医院呼吸内科,河北保定071000 [2]湖南省老年医院老年医学研究所呼吸疾病研究室

出　　处：《中国老年学杂志》2016年第23期5805-5807,共3页Chinese Journal of Gerontology

基　　金：国家自然科学基金(No.30971329)

摘　　要：目的探讨Siah2及低氧诱导因子(HIF)脯氨酰羟化酶(PHD)3的表达变化趋势在大鼠低氧性肺动脉高压(HPH)中的作用和意义。方法 40只成年雄性SD大鼠随机划分常氧正常组和低氧3 d、7 d、14 d和21 d组,每组8只,常压低氧制作HPH大鼠模型。RT-PCR检测Siah2和PHD3 mRNA表达变化,Western印迹检测上述两指标的蛋白质表达,并分析其表达变化与大鼠HPH的关系。结果常氧正常组Siah2 mRNA表达水平较低,低氧7 d后显著增高(P<0.05),低氧14 d达高峰;常氧正常组及低氧3 d组Siah2蛋白表达亦较低,低氧7 d后显著增高(P<0.05),低氧14 d达高峰。常氧正常组PHD3 mRNA和蛋白质表达均不明显,低氧3 d mRNA明显增高(P<0.05),同时随低氧时间延长其mRNA表达逐渐升高并保持在高水平;PHD3蛋白质低氧3 d明显增高(P<0.05),低氧7 d保持高水平,低氧14 d和21 d下降。相关分析表明,肺小动脉壁Siah2蛋白质表达水平与Siah2 mRNA呈正相关(r=0.87,P<0.01),与PHD3蛋白表达水平呈负相关(r=-0.44,P<0.05)。结论 Siah2与PHD3均在大鼠HPH的发病机制中发挥作用。Siah2可能从蛋白水平下调PHD3的表达水平,导致HPH的发生发展。Objective To study the dynamic expression of seven in absentia2（Siah2） and prolyl hydroxylase 3（PHD3） in rats with hypoxia-induced pulmonary hypertension（ HPH）.Methods Male SD rats（ n = 40） were randomly divided into normoxia normal,3,7,14 or 21 d hypoxia groups respectively（ n = 8）. HPH was made by atmospheric hypoxia. The expression levels of mRNA were measured by RT-PCR,Western blot was used to determine the expression of protein levels.Results Compared with normal group,Siah2 mRNA and protein levels were increased markedly after 7 d of hypoxia（ P〈0.05） and reaching its peak after 14 d of hypoxia.PHD3 mRNA was up-regulated after 3 d of hypoxia（ 0. 256 ± 0. 011,P〈0. 05）,and then remained at high levels,while PHD3 protein decreased after 14 d of hypoxia（0.204±0.022,P〈0.05）. Linear correlation analysis indicated that Siah2 protein was positively correlated with Siah2 mRNA（r= 0.87,P〈0.01） but negatively correlated with PHD3 protein（ r =-0.44,P〈0.05）.Conclusions Siah2 and PHD3 are all involved in the pathogenesis of HPH in rats. Siah2 may down-regulate PHD3 by targeting it for proteasomal degradation.

关 键 词：脯氨酰羟化酶3 Siah2 低氧性肺动脉高压 

分 类 号：R562[医药卫生—呼吸系统]