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|本期目录/Table of Contents|

慢性痛导致低氧性肺动脉功能异常

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2018年第4期
页码:
388-393
栏目:
基础研究
出版日期:
2018-04-25

文章信息/Info

Title:
Chronic pain promotes hypoxic pulmonary vascular dysfunction
作者:
杨 铮1; 刘曼玲1; 石曌玲2; 3; 殷 玥1; 2; 马 恒1; 2
（第四军医大学：1.基础部病理生理学教研室，2.基础部生理学教研室，3.西京医院小儿科，陕西 西安 710032)
Author(s):
YANG Zheng1;  LIU Man-ling1;  SHI Zhao-ling2; 3;  YIN Yue1; 2;  MA Heng1; 2
(1.Department of Physiology, 2.Department of Pathophysiology, School of Basic Medical Science; 3.Department of Pediatrics, Xijing Hospital; Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
慢性痛; 低氧性肺动脉高压; 低氧性肺血管收缩; 乙醛脱氢酶2
Keywords:
chronic neuropathic pain;  hypoxic pulmonary hypertension;  hypoxic pulmonary vasoconstriction;  aldehyde dehydrogenase 2
分类号:
R331.3
DOI:
-
文献标识码:
A
摘要:
目的 研究慢性病理性神经痛对低氧性肺动脉高压发生发展的影响及可能机制。方法 30只SD大鼠随机分为5组：常氧组、慢性痛＋常氧组、低氧组、慢性痛+低氧组和慢性痛+低氧+Alda1（乙醛脱氢酶2特异性激动剂）组，每组6只。慢性痛采用经典的大鼠背根节慢性压迫(chronic compression of dorsal root ganglia,CCD)模型。造模成功后用间断性低压低氧法建立大鼠低氧性肺动脉高压模型，然后分离大鼠三级肺小动脉，检测不同组大鼠的肺血管环舒张、收缩功能变化，同时测定各组大鼠血液循环中4-羟基壬烯酸（4-hydroxy-2-nonenal,4-HNE）的水平和肺动脉上乙醛脱氢酶(Aldehyde dehydrogenase,ALDH)2的表达。结果 低氧导致肺小动脉的舒张功能减弱(P<0.05)，收缩功能亢进；但是在慢性痛状态下，低氧组大鼠肺小动脉舒张功能进一步减弱(P<0.01)，而肺小动脉收缩功能更加亢进(P<0.01)。与此同时，低氧促进大鼠血液中4-HNE的水平升高(P<0.01)，而慢性痛+低氧组大鼠循环血液中4-HNE的水平增高更为显著(P<0.01)，提示慢性痛+低氧组大鼠肺动脉舒缩、功能异常可能是由长期慢性神经痛产生大量的4-HNE造成的。使用ALDH2的激动剂Alda1后能够显著改善慢性痛和低氧导致的肺小动脉舒张、收缩功能异常，促进肺小动脉舒张(P<0.01)，抑制收缩(P<0.01)，而且Alda-1能够显著上调慢性痛和低氧降低的ALDH2的表达(P<0.01)，减少循环血中4-HNE的水平(P<0.01)。结论 慢性病理性神经痛促进循环中4-HNE的水平增高，加重肺小动脉舒张、收缩功能异常，降低ALDH2的表达，促进低氧性肺动脉高压的发生发展。慢性神经痛可能是促进、加重低氧性肺动脉高压发生发展的诱因之一。
Abstract:
AIM To investigate the possible mechanism of the effect of chronic neuropathic pain on the development of hypoxic pulmonary hypertension. METHODS Thirty male Sprague Dawley (SD) rats were randomized into 5 groups: normoxia, chronic pain+normoxia, hypoxia, chronic pain+hypoxia, and chronic pain+hypoxia+Alda1, with 6 rats in each group. The classical chronic compression of dorsal root ganglia (CCD) model was utilized to replicate chronic neuropathic pain in the rats. After establishment of chronic neuropathic pain in all of the rats, they were exposed to a hypobaric hypoxia environment for 4 weeks to establish a hypoxic pulmonary hypertensive state. Endothelium-intact pulmonary artery rings (PAs) from all groups of rats were isolated to detect changes of relaxation and contraction. Then, circulating 4-HNE levels were recorded and expression of ALDH2 on pulmonary arteries was measured. RESULTS Hypoxia decreased diastolic function of PAs (P<0.05) and enhanced systolic function of PAs (P<0.05). Worse dysfunction of diastolic and systolic functions was seen in PAs from chronic pain+hypoxia group rats (P<0.01, respectively). Hypoxia promoted circulating 4-HNE levels (P<0.01), and circulating 4-HNE levels increased more significantly in chronic pain+hypoxia group rats (P<0.01), suggesting a large amount of 4-HNE induced by long-term chronic neuropathic pain may cause worse dysfunction of diastolic and systolic function of PAs. Use of the aldehyde dehydrogenase (Aldehyde dehydrogenase, ALDH)2 agonist Alda1 significantly improved the worse dysfunctions of diastolic and systolic function of PAs induced by chronic pain and hypoxia (P<0.01, respectively), up-regulated expression of ALDH2 (P<0.01) and decreased circulating 4-HNE levels (P<0.01). CONCLUSION Chronic neuropathic pain increased circulating 4-HNE level, decreased the expression of ALDH2 on pulmonary arteries, promoted and aggravated the dysfunctions of relaxation and contraction of PAs and therefore, accelerated development of HPH.

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备注/Memo

备注/Memo:
收稿日期：2017-10-16.基金项目：国家自然科学基金项目资助（81322004，31671424）；陕西省社发攻关项目资助（2011KJXX66，2015KW-050）通讯作者：马恒，副教授，主要从事心肌内源性保护机制研究 Email: hengma@fmmu.edu.cn 作者简介：杨铮，硕士生 Email：420319776@qq.com
更新日期/Last Update: 1900-01-01