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|本期目录/Table of Contents|

慢性病理性神经痛导致心肌线粒体功能障碍

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2017年第5期
页码:
501-505,543
栏目:
基础研究
出版日期:
2017-03-25

文章信息/Info

Title:
ALDH2 confers protection against chronic neuropathic pain-induced myocardial mitochondrial dysfunction
作者:
杨京润1; 2; 李 晨2; 薛 涵1; 2; 王一石1; 2; 杨 铮2; 殷 玥1; 2; 石曌玲1; 2; 3; 余 璐4; 马 恒1; 2
(第四军医大学:1.基础医学院生理学教研室，2.基础医学院病理生理学教研室，3.西京医院儿科，4.基础医学院病理学教研室，陕西 西安 710032）
Author(s):
YANG Jing-run1; 2;  LI Chen2;  XUE Han1; 2;  WANG Yi-shi1; 2;  YANG Zheng2;  YIN Yue1; 2;  SHI Zhao-ling1; 2; 3;  YU Lu4;  MA Heng1; 2
(1.Department of Physiology, 2.Department of Pathophysiology, 3.Department of Paediatrics, Xijing Hospital, 4.Department of Pathology, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
慢性病理性神经痛; 乙醛脱氢酶2; 去乙酰化酶3; 线粒体
Keywords:
chronic neuropathic pain;  ALDH2;  SIRT3;  mitochondria
分类号:
Q463
DOI:
-
文献标识码:
A
摘要:
目的 探讨慢性神经性病理痛对心肌线粒体功能的影响。方法 用10只C57雄性小鼠通过背根神经节(QRG)压迫3周方法建立慢性疼痛模型（Chronic compression of DRG,CCD）组；用10只小鼠做无痛对照(Con)组；另20只1月龄小鼠经尾静脉分别注射以9型腺相关病毒为载体的重组病毒,其中10只注射AAV9-CMV-ALDH2〔3×1011viral genomes（vg）/只,病毒基因组〕上调乙醛脱氢酶（ALDH）2的蛋白表达，剩余10只注射AAV9-CMV-GFP（绿色荧光蛋白）为病毒对照。4周后，ALDH2稳定过表达之后，再建立CCD模型(CCD+ALDH2)组。慢性疼痛3周后提取心肌组织，用荧光探针检测心肌内活性氧自由基（ROS）的水平；用美国Sigma公司试剂盒测定丙二醛（MDA）的含量；用免疫共沉淀方法（Co-IP）测定心肌中锰超氧化物歧化酶（MnSOD）的乙酰化水平和去乙酰化酶（SIRT）3的羰基化水平；用美国Cayman公司试剂盒检测MnSOD的活性。结果 慢性疼痛导致小鼠心肌氧化应激水平和脂质过氧化损伤显著增加，线粒体膜电位较对照组降低（P<0.05）；慢性痛小鼠心肌中线粒体抗氧化酶MnSOD乙酰化程度较对照组增加，活性减退（均P<0.05）。上述结果提示：慢性痛可导致心肌线粒体功能受损。进一步分析机制发现，慢性痛小鼠血浆中的活性羰基类物质4-羟基壬烯醛（4-HNE）较对照组显著增加（P<0.05），导致心肌线粒体去乙酰化酶SIRT3被羰基化修饰。上调ALDH2表达可有效的抑制慢性痛导致的心肌蛋白质羰基应激，减轻疼痛，有效保护心肌线粒体功能。结论 慢性疼痛可诱发心肌羰基应激导致线粒体功能障碍，上调ALDH2可有效抑制疼痛并保护心肌线粒体功能。
Abstract:
AIM To investigate the effects of chronic neuropathic pain (CNP) on the function of myocardial mitochondria. METHODS Forty male C57 mice were used in the present study. Ten mice were used to establish chronic neuropathic pain model using chronic compression of dorsal root ganglion (CCD). Ten mice were regardedas control group (Con). Ten mice of one month were injected with AAV9-CMV-ALDH2 (3×1011 vg per mice) via vena caudalis. Ten mice of one month injected with AAV9-CMV-GFP via vena caudalis were regarded as the negative control. After 4 weeks, ALDH2 was over-expressed stably, and CCD model was established (CCD+ALDH2). After 3 weeks of CCD, the myocardial tissues were extracted. Detected the levels of reactive oxygen species (ROS), malondialdehyde (MDA), the activity and acetylation of MnSOD, and the activity and carbonylation of SIRT3. RESULTS CNP dramatically increased mitochondrial oxidative stress and lipid peroxidation, and decreased mitochondrial membrane potential in mice myocardium. The acetylation of MnSOD increased significantly in CNP mice (P<0.05), leading to the decreased activity (P<0.05). The results mentioned above suggested that CNP triggered mitochondrial dysfunction in the myocardium. Furthermore, the serum level of 4-hydroxynonenal (4-HNE) increased markedly (P<0.05), resulting in the carbonylation of SIRT3. The up-regulation of ALDH2 significantly attenuated CNP-induced carbonyl stress and pain (P<0.05), and maintained mitochondrial function. CONCLUSION CNP induces myocardial carbonyl stress and mitochondrial dysfunction. The up-regulation of ALDH2 effectively mitigates pain and myocardial mitochondrial dysfunction.

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备注/Memo

备注/Memo:
收稿日期：2017-01-10.
基金项目：国家自然科学基金项目资助（31671424，31571413，81322004）
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：杨京润，硕士生 Email：444356009@qq.com
更新日期/Last Update: 2017-04-20