摘要： 目的 探讨过氧化物酶体增殖物激活受体α（PPARα）在肥胖大鼠神经病理性疼痛中的作用及其机制。方法 SPF级SD大鼠60只，随机分为6组：高脂（HF）组、HF+坐骨神经分支损伤（SNI）组、HF+SNI+PPARα激动剂（PEA）组、HF+SNI+PPARα抑制剂（GW6471）组、低脂（LF）组、LF+SNI组，连续高脂或低脂饲料喂养12周，采用SNI制作大鼠神经病理性疼痛模型，HF组、LF组、HF+SNI组、LF+SNI组监测机械刺激缩爪潜伏期（PWT）14 d，HF+SNI+PEA组、HF+SNI+G6471组监测PWT 7 d，Western blotting检测各组大鼠脊髓组织中PPARα、Bax及Bcl-2蛋白的表达。结果 与LF大鼠比较，HF大鼠6周发生肥胖；中枢神经系统（CNS）中PPARα蛋白、Bcl-2表达显著降低，Bax表达显著提高（P<0.05）。与HF组大鼠比较，HF+SNI组大鼠CNS中PPARα蛋白、Bcl-2表达下调，Bax表达上调（P<0.05）。与HF+SNI大鼠组比较，HF+SNI+PEA组PWT显著增加，上调PPARα、Bcl-2表达，下调Bax蛋白表达（P<0.05）；与HF+SNI比较，HF+SNI+G6471组大鼠PWT降低、PPARα及Bcl-2的表达下调、Bax蛋白的表达上调（均P<0.05）。结论 HF诱导的SNI大鼠CNS中PPARα活性降低，PPARα蛋白可能成为预防和治疗肥胖相关神经病理性疼痛的新靶点。

PPARα对肥胖大鼠神经病理性疼痛的作用及其机制

郭欣欣¹, 张博涵², 赵梦楠², 王品莹², 陶学恕²

1. 锦州医科大学附属第三医院麻醉科, 辽宁 锦州 121000;
2. 中国医科大学附属第一医院疼痛科, 沈阳 110001

收稿日期:2019-04-02出版日期:2020-02-29发布日期:2019-12-26
通讯作者:郭欣欣E-mail:mzguoxx@163.com
作者简介:郭欣欣(1981-),女,主治医师,硕士.
基金资助:辽宁省自然科学基金（20180550175）


关键词: 肥胖, 大鼠, 神经病理性疼痛, 过氧化物酶体增殖物激活受体α, 细胞凋亡
Abstract: Objective To investigate the role of peroxisome proliferators activate receptors α (PPARα)in neuropathic pain and its relationship with apoptosis in obese rats. Methods Sixty SPF grade SD rats were randomly divided into 8 groups:high fat(HF) group,HF + spared nerve injury (SNI) group,HF + SNI + PPARα agonist (PEA) group,HF + SNI + PPARα inhibitor (GW6471) group,low fat (LF) group,LF + SNI group. high-fat or low-fat diet for 12 weeks. Neuropathy pain model rats were made by damaging a branch of the sciatic nerve. HF,LF, HF + SNI,LF + SNI groups at paw withdrawl threshold(PWT)14 d,PWT 7 d were monitored for depressions in the PPARα agonist and the PPARα inhibitor groups. The expressions of PPARα,Bax and Bcl-2 in the spinal cord tissues of rats in each group,were detected by Western blotting. Results Compared to LF rats,HF rats were obese after 6 weeks. The expressions of PPARα protein and Bcl-2 in the central nervous system(CNS)were significantly decreased,and the expressions of Bax were significantly increased(P<0.05). Compared to the HF group,the expressions of PPARα protein and Bcl-2 in the CNS in the HF+SNI group were down-regulated,and the expressions of Bax were up-regulated(P<0.05). Compared to the HF+SNI group,the HF+SNI+PEA group significantly increased PWT,up-regulated PPARα and Bcl-2 expressions,and down-regulated Bax protein expressions(P<0.05). Compared to the HF+SNI group,PWT of the HF+SNI+G6471 group decreased,the expressions of PPARα and Bcl-2 were down-regulated,and the expressions of Bax protein were up-regulated(all P<0.05). Conclusion The expression of PPARα in HF-induced obese rats is down-regulated,and the neuronal apoptosis caused by neuronal injury is enhanced by regulating the apoptosis of CNS cells. The regulation of apoptosis in the CNS may be a new way to prevent and treat obesity-related neuropathic pain.
Key words: obesity, rats, neuropathic pain, peroxosome proliferator activated receptor α, cell apoptosis
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