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脂肪因子CTRP9对低氧性肺动脉高压大鼠肺血管的舒张作用及其机制

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2016年第1期
页码:
1-006
栏目:
基础研究
出版日期:
2015-09-15

文章信息/Info

Title:
Vasodilation effect and its mechanism of C1q/TNF-related-protein-9 on pulmonary arteries of hypoxic pulmonary hypertensive rat
作者:
杨 瑞1; 张存娟1; 邢文娟2; 梁向艳3; 苏 慧4; 张海锋3; 孙 新1
（第四军医大学：1.西京医院儿科，2.基础部生理学教研室，3.基础部教学实验中心，4.西京医院老年病科，陕西 西安 710032）
Author(s):
YANG Rui1;  ZHANG Cun-juan1;  XING Wen-juan2;  LIANG Xiang-yan3;  SU Hui4;  ZHANG Hai-feng3;  SUN Xin1
(1.Department of Pediatrics, 4.Department of Geriatrics, Xijing Hospital, 2.Department of Physiology, 3.Experiment Teaching Center, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
低氧性肺动脉高压; 内皮功能障碍; 脂肪因子CTRP9; 大鼠
Keywords:
hypoxic pulmonary hypertension;  endothelial dysfunction;  adipokines C1q/TNF-related-protein-9;  rat
分类号:
R543.2
DOI:
-
文献标识码:
A
摘要:
目的 观察脂肪因子C1q/肿瘤坏死因子相关蛋白9（CTRP9）对于低氧性肺动脉高压（HPH）大鼠离体肺动脉的舒张作用，并探讨其可能的分子机制。方法 将24只雄性SD大鼠随机分为对照组、HPH 2周组和HPH 4周组，每组8只。对照组动物在正常环境中饲养，低氧组动物按低压低氧法建立HPH模型。模型建立后，用右心导管法测定肺动脉平均压（mPAP）、右心室平均压（mRVP），称质量测量右心室/(左心室+室间隔)〔RV/(LV+S)〕、右心室/体质量（RV/BW）；ELISA法检测血清NO和CTRP9水平；HE染色高倍镜下观察肺小动脉显微结构改变。取大鼠左、右肺动脉干制备血管环，行离体灌流实验，观察不同浓度CTRP9的舒张血管作用；收集作用于血管环的灌流液，检测NO产物。收集剩余的肺动脉血管组织，分组后用不同浓度CTRP9孵育，部分组别孵育前加入Compound C或L-NAME，然后行Western blot检测pAMPK/AMPK、pAkt/Akt、peNOS/eNOS等信号蛋白分子。结果 与对照组比，HPH组大鼠的mPAP、mRVP、RV/(LV+S)、RV/BW均显著增高（P<0.01），且血清NO、CTRP9水平下降（P<0.05,P<0.01）。病理切片显示HPH组大鼠肺动脉平滑肌和弹力纤维层增生，血管壁增厚，管腔狭窄、变形。选取对乙酰胆碱和硝普钠有良好舒张反应的血管环，加入CTRP9后血管环明显舒张，预先加入Compound C或L-NAME组，CTRP9舒血管作用被显著抑制；血管环组织AMPK、Akt和eNOS磷酸化水平、灌流液NO产物增加（P<0.05，P<0.01）。结论 HPH时血管内皮功能受损，CTRP9有明显的舒张血管作用，其机制可能与增加AMPK/Akt/eNOS磷酸化和NO释放有关。
Abstract:
AIM To observe the vasodilation effects of CTRP9 on isolated rat pulmonary arteries from hypoxic pulmonary hypertension (HPH) rats and to investigate the potential molecular mechanisms. METHODS Twenty-four male Sprague Dawley (SD) rats were randomly grouped by eight each for control group, HPH 2-week group and HPH 4-week group. SD rats in the control group were fed under normal conditions, and HPH models in HPH groups were established by hypoxia method. Mean pulmonary average pressure (mPAP) and mean right ventricle pressure (mRVP) were measured by right cardiac catheterization, right ventricle/left ventricle+ventricular septum ［RV/(LV+S)］ and right ventricle/body weight were weighed. Levels of serum NO and CTRP9 were gauged by ELISA method. Microstructure development of pulmonary arteriole was observed by hematoxylin-eosin (HE) staining at high magnification and diastolic influence of different CTRP9 concentrations was observed by preparing vascular circles from left and right pulmonary trunks by isolated perfusion experiment. Perfusion liquid from affected vascular rings was collected to detect NO content and rest of pulmonary vascular tissue was collected and grouped to incubate with different levels of CTRP9, and pAMPK/AMPK, pAkt/Akt and peNOS/eNOS were measured by Western blot after Compound C or L-NAME was added into some HPH groups prior to incubation. RESULTS In comparison with those in the control group, mPAP, mRVP, RV/(LV+S) and RV/BW in HPH groups increased significantly (P<0.01) and levels of serum NO and CTRP9 decreased (P<0.05, P<0.01). Pathological section showed hyperplasia of smooth muscle and elastic fibers, pulmonary and blood vessel wall thickening and vessel narrowing with distortion in HPH groups. Significant relaxation effect was observed from CTRP9 influenced vascular rings, which had good relaxation responses to acetylcholine and sodium nitroprusside. But the relaxation effect was inhibited by Compound C or L-NAME pretreatment. Perfusate NO product increased in CTRP9 influenced vessel tissues (P<0.05). Significant increases of pAMPK/AMPK, pAkt/Akt and peNOS/eNOS in CTRP incubated vessel tissues were observed. CONCLUSION Vascular endothelial dysfunction existed when HPH, CTRP9 has a remarkable vasodilation effect.

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备注/Memo

备注/Memo:
收稿日期：2015-05-26.
>基金项目：国家自然科学基金项目资助（81270330，30700345，31371151，31271219）;陕西省科技厅国际合作课题项目资助（2013KW30-02）;陕西省科学技术研究发展计划项目资助（2013KJXX-89）
通讯作者：孙新，副教授，主要从事肺动脉高压研究 Email: sunxin6@fmmu.edu.cn
>共同通讯作者：张海锋，副教授，主要从事心血管生理学研究 Email:hfzhang@fmmu.edu.cn
作者简介：杨瑞，硕士生Email:yangr029@126.com
更新日期/Last Update: 2015-09-16