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间歇性低压低氧预适应延缓大鼠低氧性肺动脉高压发展并改善肺动脉舒张

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2016年第6期
页码:
647-650,670
栏目:
基础研究
出版日期:
2016-07-05

文章信息/Info

Title:
Alleviation effect of intermittent hypobaric hypoxia preconditioning on hypoxic pulmonary artery hypertension and improvement of pulmonary artery vasodilatation in rats
作者:
杨 瑞1; 张海锋2; 孙 新1; 邢文娟3; 苏 慧4; 陈健康2
（第四军医大学：1.西京医院儿科，2.教学实验中心，3.生理学教研室，4.西京医院老年病科，陕西 西安 710032）
Author(s):
YANG Rui1;  ZHANG Hai-feng2;  SUN Xin1;  XING Wen-juan3;  SU Hui4;  CHEN Jian-kang2
(1.Department of Pediatrics, Xijing Hospital, 2.Experimental Teaching Center, 3.Department of Physiology, 4.Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
间歇性低压低氧预适应; 低氧性肺动脉高压; 右心重构; 血管舒张功能; 大鼠
Keywords:
intermittent hypobaric hypoxia preconditioning;  hypoxic pulmonary artery hypertension;  right ventricle restricting;  artery vasodilatation;  rat
分类号:
R543.2
DOI:
-
文献标识码:
A
摘要:
目的 观察间歇性低压低氧预适应对大鼠低氧性肺动脉高压（HPH）及肺动脉舒张功能的影响。方法 将24只雄性SD大鼠随机分为：对照组、HPH组、间歇性低压低氧预适应组，每组8只。对照组动物常规饲养10周；HPH组动物先在同一室内常规饲养6周，然后按低压低氧法建立HPH模型（给予持续低压低氧4周）；间歇性低压低氧预适应组动物先给予预适应实验：HPH 1周，再放置同一室内常规饲养1周，如此重复循环3个周期共6周，然后按低压低氧法建立HPH模型（方法同HPH组）。分组模型建立后，用右心导管法测定肺动脉平均压（mPAP）、右心室平均压（mRVP）；称重测量右心室/（左心室+室间隔）〔RV/(LV+S)〕、右心室/体质量（RV/BW）；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，行离体血管灌流实验，观察不同浓度乙酰胆碱和硝普钠的舒张血管作用。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）；病理切片显示低氧后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；且低氧后大鼠肺动脉血管环对乙酰胆碱的舒张作用显著降低（P<0.01）。与HPH组比，经间歇性低压低氧预适应处理的大鼠mPAP、mRVP、RV/(LV+S)、RV/BW均显著降低（P<0.05）；病理切片显示肺动脉平滑肌和弹力纤维层增生及血管壁增厚有所缓解；且肺动脉血管环对乙酰胆碱的舒张作用显著增强（P<0.05）。结论 间歇性低压低氧预适应可增强大鼠肺动脉对低压低氧环境的耐受能力，延缓肺动脉高压和右心重构的发展，并改善肺动脉内皮功能。
Abstract:
AIM To observe the effect of intermittent hypobaric hypoxia preconditioning on hypoxic pulmonary artery hypertension (HPH) and vasodilatation of pulmonary artery in rats. METHODSTwenty-four male Sprague Dawley rats were randomly divided into control group, HPH group and intermittent hypobaric hypoxia preconditioning group (n=8 in each group). Rats in control group were fed under normal conditions for 10 weeks and rats in HPH group were fed under normal condition with rats in control group for 6 weeks and then HPH models were established by hypoxia method (under condition of hypobaric hypoxia for the following 4 weeks). Rats in intermittent hypobaric hypoxia preconditioning group were pre-conditioned: fed in HPH for 1 week, fed in normal condition for another week, and repeated the process three times (total of 6 weeks). The same HPH models as those in HPH group were then established by hypoxia method (under condition of hypobaric hypoxia for the remaining 4 weeks). Mean pulmonary average pressure (mPAP) and mean right ventricle pressure (mRVP) were measured by right cardiac catheterization, and right ventricle/left ventricle+ventricle spectrum (RV/LV+S) and right ventricle/body weight were weighed. Microstructural development of pulmonary arteriole was observed by hematoxylin-eosin (HE) stained at high magnification and diastolic influence of different acetylcholine and sodium nitroprusside concentrations were observed by preparing a vascular circle from left and right pulmonary trunks by isolated perfusion experiment. RESULTSIn comparison with those in the control group, mPAP, mRVP, RV/(LV+S) and RV/BW in HPH group increased significantly (P<0.01). Histopathological section showed hyperplasia of smooth muscle and elastic fibers, pulmonary and blood vessel wall thickening and vessel narrowing with distortion in HPH group. The relaxation effect of acetylcholine was significantly reduced on HPH conditioned pulmonary vascular rings (P<0.01). In comparison with HPH group, mPAP, mRVP, RV/(LV+S) and RV/BW in intermittent hypobaric hypoxia preconditioned group was markedly reduced (P<0.05). Pathological section showed alleviation of hyperplasia of smooth muscle and elastic fibers, pulmonary and blood vessel wall thickening and vessel narrowing with distortion. The relaxation effect of acetylcholine on pulmonary vascular rings (P<0.05) was significantly increased. CONCLUSIONIntermittent hypobaric hypoxia preconditioning increases the tolerance of pulmonary artery under hypobaric hypoxia environment, alleviates pulmonary artery hypertension and restructuring of right ventricle and improves endothelial function of the pulmonary artery.

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备注/Memo

备注/Memo:
收稿日期：2016-01-26.
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 作者介绍：杨瑞，硕士生Email:yangr029@126.com
更新日期/Last Update: 2016-07-10