CTRP9抑制低氧环境下肺微血管内皮细胞IL-6和TNF-α表达的研究  

CTRP9 inhibits expressions of IL-6 and TNF-α in pulmonary microvascular endothelial cell under hypoxia condition

作　　者：金巧艳 曾明华[1] 谭延振[2] 苏慧[3] 易蔚[2] 张海锋[4] 孙新[1] 

机构地区：[1]第四军医大学西京医院儿科,陕西西安710032 [2]第四军医大学西京医院心血管外科,陕西西安710032 [3]第四军医大学西京医院老年病科,陕西西安710032 [4]第四军医大学教学实验中心,陕西西安710032

出　　处：《心脏杂志》2017年第4期399-404,共6页Chinese Heart Journal

基　　金：国家自然科学基金资助(81670449;31371151;31271219);陕西省国际合作课题项目资助(2013KW30-02)

摘　　要：目的研究低氧环境下C1q肿瘤坏死因子相关蛋白9(C1q/TNF-related protein 9,CTRP9)对肺微血管内皮细胞(Pulmonary microvascular endothelial cell,PMVEC)中白介素(IL)-6、肿瘤坏死因子(TNF)-α表达的影响。方法将雄性SD大鼠随机分为常氧组、低氧组,采用低压低氧法建立大鼠低氧性肺动脉高压(Hypoxic pulmonary hypertension,HPH)模型,28 d后检测各组大鼠血流动力学、右心室肥厚指标和组织病理学改变;用RT-PCR检测HPH大鼠肺组织中IL-6、TNF-αmRNA表达水平;用ELISA法检测二者在血清中的变化。分离培养健康雄性SD大鼠的PMVEC,分别在常氧(210 ml/L O_2、50 ml/L CO_2)、低氧(50 ml/L O_2、50 ml/L CO_2)、或者低氧+CTRP9(5μg/ml)环境中孵育48 h。结果与常氧组相比,低氧组大鼠右心室收缩压和右心室肥厚指标增加(P<0.05),肺小动脉管壁增厚,显示造模成功;肺组织中IL-6、TNF-αmRNA水平上调(P<0.05),两种炎症因子在血清中的含量增加(P<0.05)。与常氧组相比,低氧处理使两种炎症因子IL-6、TNF-α在PMVEC中mRNA水平及在细胞培养上清中的含量均增加(P<0.05);在低氧的同时给予CTRP9孵育时,与单纯低氧组相比,两种炎症因子在PMVEC中mRNA水平及在细胞培养上清中的含量均降低(P<0.05)。结论大鼠发生HPH时,炎症因子IL-6、TNF-α表达升高。而CTRP9对低氧条件下PMVEC表达和分泌IL-6及TNF-α具有抑制作用,进而有望预防或延缓HPH的发生发展。AIM To investigate the effects of CTRP9 on hypoxia-induced expressions of interleukin-6 （IL-6） and tumor necrosis factor alpha （TNF-et） in pulmonary microvascular endothelial cells （PMVECs）. METHODS SD rats were randomly divided into normoxic group and hypoxic group. The rats in the hypoxic group were exposed to low-pressure and low-oxygen condition in an auto-modulating hypobaric and hypoxic cabin （air pressure 55 kPa, oxygen concentration 10% ） for 28 days to establish the animal model of hypoxic pulmonary hypertension （HPH）. The histopathological change, the hemodynamic index and the right ventricular hypertrophy index of rats were detected. The mRNA levels of IL-6 and TNF-a in lungswere determined by RT-PCR and serum IL-6 and TNF-a were measured by ELISA. Primary PMVEC were cultured under normoxia, hypoxia （50 ml/L 02 ） or hypoxia with CTPR9 treatment and mRNA of IL-6 and TNF-a in the cell lysate was determined by RT-PCR. RESULTS In the hypoxia group, the right ventricular systolic pressure, the right ventricular hypertrophy index and the thickness of pulmonary arterial wall were increased compared with those in the normoxia group （ P 〈 0. 05 ）. The expressions of IL-6 and TNF-a in PMVEC increased significantly under hypoxia environment （ P 〈 0. 05 ） and CTRP9 treatment effectively inhibited the increase （P 〈 0. 05 ）. CONCLUSIONS The expressions of IL-6 and TNF-a increase in HPH rats. CTRP9 could effectively inhibit the expressions and secretions of inflammatory cytokines IL-6 and TNF-a in PMVEC in hypoxia condition, which makes CTRP9 a potential therapy to prevent and limit the development of HPH.

关 键 词：C1q肿瘤坏死因子相关蛋白9 低氧性肺动脉高压 肺微血管内皮细胞 白介素-6 肿瘤坏死因子-α 

分 类 号：R543.2[医药卫生—心血管疾病]