弥可保预防长春新碱诱导的病理性疼痛的机制  

The Mechanism of Methylcobalamin in Preventing Pain Hypersensitivity Induced by Vincristine

作　　者：黄睿臻 徐劲[1] 魏绪红[1] HUANG Rui-zhen;XU Jin;WEI Xu-hong(Department of Physiology and Pain Research Center,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou 510080,China)

机构地区：[1]中山大学中山医学院生理教研室//疼痛研究中心,广东广州510080

出　　处：《中山大学学报（医学科学版）》2022年第2期212-220,共9页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(81870969,81471250);广东省自然科学基金(2019A1515011855)。

摘　　要：【目的】观察弥可保对长春新碱诱导的病理性疼痛大鼠脊髓背角突触传递功能的影响并探讨其机制。【方法】SD大鼠随机进行如下分组:生理盐水组、生理盐水+弥可保组、长春新碱组、长春新碱+弥可保组,Up-down方法测定50%机械撤足阈值,在体电生理方法记录脊髓背角C纤维诱发电位的幅度,免疫组化检测脊髓背角CGRP阳性纤维末梢的数量,免疫组化或Western blot检测NF-κB信号p65及IL-10蛋白表达的情况。【结果】长春新碱可引起机械痛敏(P<0.05),同时引起脊髓背角C纤维诱发电位幅度明显增大(P<0.05)。长春新碱导致脊髓背角CGRP阳性纤维的芽生(P<0.01)、NF-κB信号通路激活(P<0.001),并可降低IL-10的表达(P<0.01)。给予弥可保可阻断长春新碱所引起的上述变化(P<0.05)。【结论】弥可保可预防长春新碱诱导的病理性疼痛,其作用可能是通过降低CGRP阳性纤维芽生、平衡炎性因子表达,进而减弱中枢敏感化而进行的。【Objective】To investigate whether methylcobalamin(McB)affects the spinal synaptic transmission in rats with neuropathic pain after vincristine(VCR)treatment and to elucidate the mechanisms.【Methods】Rats were randomly separated into the following groups:Saline,Saline+McB,VCR,VCR+McB.The 50%paw withdrawal threshold was mea⁃sured by the up-down method,C-fiber evoked field potentials were measured via electrophysiological recording.Expres⁃sion of CGRP,p-p65 and IL-10 was detected by Western blot or immunofluorescence.【Results】Intraperitoneal injection of Vincristine(0.1mg/kg,daily for 10 days)induced mechanical allodynia(P<0.05),increased the amplitude of C-fiber evoked field potentials(P<0.05),and increased the expression of CGRP(P<0.01)and p-p65(P<0.001),whereas de⁃creased the expression of IL-10(P<0.01)in the spinal dorsal horn.Intraperitoneal injection of McB,the activated form of vitamin B12,decreased the amplitude of C-fiber evoked field potentials(P<0.01)and the spinal expression of CGRP(P<0.01)and p-p65(P<0.01)after vincristine treatment.Additionally,the IL-10 expression was augmented followed by McB treatment in rats subjected to chronic VCR injections(P<0.05).【Conclusion】McB prevented the central sensitization following vincristine injection,possibly by decreasing the expression of CGRP and p-p65 and increasing the expression of IL-10.

关 键 词：痛觉过敏 长春新碱 弥可保 C纤维 长时程增强 突触可塑性 

分 类 号：R54[医药卫生—心血管疾病]