内吗啡肽2对神经病理性痛大鼠背根神经节内μ-阿片受体表达的影响  

Effect of endomorphin 2 on expression ofμ-opioid receptors in the dorsal root ganglion in rats with neuropathic pain

作　　者：谢雨杉 刘海帆 孙騊 万法萍 Xie Yushan;Liu Haifan;Sun Tao;Wan Faping(Dept of Human Anatomy,Xuzhou Medical University,Xuzhou 221004)

机构地区：[1]徐州医科大学人体解剖学教研室,徐州221004

出　　处：《安徽医科大学学报》2023年第11期1833-1840,共8页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81801104)。

摘　　要：目的探讨在内吗啡肽2(EM2)的镇痛过程中,μ-阿片受体(MOR)的表达变化及胞内囊泡转运对其变化的影响。方法成年雄性SD大鼠,随机分为3组:正常对照组、病理性痛组和药物组,病理性痛为坐骨神经分支选择性损伤(SNI)诱导的神经病理性痛(NP)。药物组为鞘内注射EM2的NP大鼠。采用免疫荧光单标染色和免疫印迹方法检测MOR总蛋白和磷酸化蛋白以及Rab7蛋白表达量的变化,采用免疫荧光双标染色方法检测MOR/Rab7和MOR/LAMP1免疫阳性标志物的表达变化。结果与正常对照组比较,病理性痛组大鼠背根神经节(DRG)内MOR总蛋白和磷酸化蛋白的表达量降低(P<0.05),Rab7蛋白的表达量明显增高(P<0.05);MOR/Rab7免疫阳性标志物占Rab7或MOR、MOR/LAMP1免疫阳性标志物占LAMP1或MOR阳性标志物的比例均增高(P<0.05)。鞘内多次注射EM2后,病理性痛大鼠的后足缩足反应阈值明显增高(P<0.01),DRG内MOR总蛋白和磷酸化蛋白的表达量增高(P<0.05),Rab7的表达量降低(P<0.05)。MOR/Rab7阳性双标产物占Rab7或MOR阳性标志物、MOR/LAMP1阳性双标产物占LAMP1或MOR阳性标志物比例均降低(P<0.05)。结论在镇痛过程中,EM2抑制SNI的NP大鼠DRG内Rab7的表达,减少MOR向溶酶体运输,促进MOR复敏。Objective To explore the expression of theμ-opioid receptor(MOR)and the effects of intracellular vesicle transport on the MOR expression during endomorphin 2(EM2)analgesia.Methods Adult male SD rats were randomly divided into 3 groups:control(naive)group,neuropathic pain group and drug group.Spared nerve injury(SNI)induced neuropathic pain rats were employed as the pain model.The drug group rats were the SNI pain ones intrathecally injected with EM2.The methods of immunofluorescence single staining and Western blot were used to detect the expression of MOR total protein,phosphorylated protein and Rab7 protein.Immunofluorescence double staining was used to detect the expression of MOR/Rab7 and MOR/LAMP1 co-labeled immunoreactivity.Results Compared with the control group,the expression of total MOR protein and phosphorylated protein in the dorsal root ganglion(DRG)of the SNI pain rats decreased(P<0.05),and the expression of Rab7 significantly increased(P<0.05).The expression of MOR/Rab7 co-labeled immunoreactivity in Rab7 and MOR immunoreactive(-ir)products and MOR/LAMP1 co-labeled immunoreactivity in MOR and LAMP1-ir products both increased(P<0.05).Multiple intrathecal injection of EM2 significantly increased paw withdrawal threshold in the SNI neuropathic pain rats(P<0.01),the expression of MOR protein and phosphorylated protein in DRG was increased(P<0.05),while the expression of Rab7 decreased(P<0.05).Compared with the control group,the expression of MOR/Rab7 positive products in Rab7 and MOR positive ones decreased,and the expression of MOR/LAMP1 positive products in LAMP1 and MOR positive markers decreased(P<0.05).Conclusion In the process of analgesia,EM2 inhibits the expression of Rab7 in the DRG of SNI neuropathic pain rats,reduces the transport of MOR to lysosomes,and promotes the re-sensitization of MOR.

关 键 词：内吗啡肽-2 Μ-阿片受体 背根神经节 神经病理性痛 囊泡运输 

分 类 号：R745.4[医药卫生—神经病学与精神病学]