抵抗素样分子β和NADPH氧化酶4在低氧性肺动脉高压大鼠肺小动脉的表达变化及意义  

Expressions and evaluation of resistin-like molecule β and nicotinamide-adenine dinucleotide phosphate oxidase 4 in pulmonary arteries of rats with hypoxia induced pulmonary hypertension

作　　者：田禾燊 戴爱国[1] 胡瑞成[1] 蒋永亮[1] 朱黎明[1] 娄华英 Tian Heshen;Dai Aiguo;Hu Ruicheng;Jiang Yongliang;Zhu Liming;Lou Huaying(Department of Respiratory Medicine,Hunan Provincial People＇s Hospital,Changsha 410000,China)

机构地区：[1]湖南省人民医院呼吸内科,长沙410000

出　　处：《国际呼吸杂志》2018年第16期1243-1249,共7页International Journal of Respiration

基　　金：国家自然科学基金（81270118、81570052）

摘　　要：目的研究大鼠低氧性肺动脉高压（HPH）肺小动脉平滑肌抵抗素样分子β（RELM-β）和NADPH氧化酶4（NOX4）表达变化及与血管重塑的关系。方法40只雄性SD成年大鼠随机分为对照组（C组）、低氧3d、7d、14d和21d组（H3、H7、H14、H21组），复制HPH大鼠模型；测各组大鼠平均肺动脉压（mPAP）、右室肥厚指数（RVHI）；取左肺组织包埋切片HE染色观察血管形态学指标；免疫组织化学检测血管壁RELM-β和NOX4蛋白表达；实时荧光定量聚合酶链式反应检测肺小动脉平滑肌中RELMG和NOX4mRNA表达情况。结果与对照组相比，低氧组大鼠出现肺小动脉重塑和RVHI增加，21d时最明显；低氧7d后，mPAP上升，14d达高峰并持续到21d；mRNA显示RELM—β和NOX4在对照组肺小动脉壁弱阳性表达；RELM—β mRNA于低氧7d后明显增加，低氧14d后达高峰，低氧21d下降但仍高于对照组；NOX4mRNA于低氧3d明显增加，低氧7d下降但高于对照组，低氧21d再次升高且高于低氧3d组，呈“驼峰样”改变。免疫组织化学显示RELM—β和NOX4变化趋势与mRNA水平变化基本一致；大鼠肺小动脉壁RELM—β与NOX4mRNA、蛋白表达与mPAP、血重塑指数、RVHI均呈正相关。结论慢性低氧诱导HPH大鼠模型肺小动脉壁REI，M—β、NOX4表达升高，RELMp可能促进NOX4在慢性低氧后期的表达增加，二者共同参与HPH的发病过程。Objective To investigate the dynamic expression and effect of Siahl in the pulmonary arterioles in different phases of rats with hypoxic pulmonary hypertension （HPH）. Methods Forty adult male Wistar rats were randomly divided into 5 groups, 8 rats in each group, and exposed to normoxia （Control group） or exposed to hypoxia for 3 d, 7 d, 14 d or 21 d, respectively. The HPH models were established by normobaric intermittent hypoxia. Mean pulmonary arterial pressure （mPAP）, right ventricle hypertrophy index （RVHI）, and vessel morphometry were measured. Reverse transcriptasepolymerase chain reaction and in situ hybridization were used to determine the mRNA expression of Siahl. Immunohistochemistry and Western blot were used to determine the protein expression of resistiw like molecule β （RELM -β） and nicotinamide-adenine dinucleotide phosphate oxidase 4 （NADPH oxidase 4, NOX4）. Results The hypoxic rats developed pulmonary vascular remodeling in pulmonary arterioles after 7 d of hypoxia. Pulmonary vascular remodeling in pulmonary arterioles was significantly increased after 14 d of hypoxia. The level of mPAP in hypoxic rats was increased significantly after 7 d of hypoxia, and reached to its peak after 14 d of hypoxic exposure. RVHI was markedly increased after 14 d of hypoxia. RELM-β, NOX4 mRNA and protein staining were poor in pulmonary arteriole walls of the control rats, hut were markedly increased after 3 d and 14 d of hypoxia, then declined a little after 21 d of hypoxia. Linear correlation analysis showed that RELM-β, NOX4 proteins was positively correlated with RELM-β, NOX4 mRNA. REI.M-β, NOX4 mRNA and proteins were positively correlated with mPAP, pulmonary vascular remodeling index and RVHI. Conclusions Under chronic hypoxia, RELM-β, NOX4 is transcriptionally induced in pulmonary arterioles, and may be involved in the pathogenesis of HPH in rat.

关 键 词：抵抗素样分子β NADPH氧化酶4 低氧性肺动脉高压 基因表达 

分 类 号：R544.1[医药卫生—心血管疾病]