PPARα对肥胖大鼠神经病理性疼痛的作用及其机制  

Effect of PPARα on neuropathic pain in obese rats and its mechanism

作　　者：郭欣欣 张博涵 赵梦楠[2] 王品莹 陶学恕 GUO Xinxin;ZHANG Bohan;ZHAO Mengnan;WANG Pinying;TAO Xueshu(Department of Anesthesiology,The Third Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000,China;Department of Pain Medicine,The First Hospital,China Medical University,Shenyang 110001,China)

机构地区：[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

出　　处：《中国医科大学学报》2020年第2期124-128,共5页Journal of China Medical University

基　　金：辽宁省自然科学基金(20180550175)

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。Objective To investigate the role of peroxisome proliferators activate receptorsα(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+PPARαagonist(PEA)group,HF+SNI+PPARαinhibitor(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 PPARαagonist and the PPARαinhibitor 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 PPARαprotein 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 PPARαprotein 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 PPARαand 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 PPARαand Bcl-2 were down-regulated,and the expressions of Bax protein were up-regulated(all P<0.05).Conclusion The expression of PPARαin 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.

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 

分 类 号：R745[医药卫生—神经病学与精神病学]