摘要
目的探究纳布啡对神经病理性疼痛(NP)模型大鼠的痛觉敏化及脊髓一氧化氮/环鸟苷单磷酸(NO/cGMP)通路的影响。方法建立NP大鼠模型,并将造模成功的30只大鼠随机分为NP组、纳布啡+NP组、纳布啡+7-硝基吲唑(7-N1)+NP组,每组各10只;另取10只大鼠,仅暴露L5横突,但不结扎脊神经,作为假手术(Sham)组。药物干预后,利用机械性刺激缩足实验检测大鼠机械痛敏;缩爪热潜伏期实验检测热缩足反射潜伏期(PWTL);ELISA法检测脊髓中IL-6、IL-1β表达水平;免疫荧光染色检测脊髓背角中小胶质细胞标志物Iba-1表达;蛋白质印迹法检测Iba-1及NO/cGMP信号通路相关蛋白表达水平。结果与Sham组相比,NP组大鼠机械刺激缩足反射阈值(PWMT)和PWTL均降低,IL-6、IL-1β水平、Iba-1荧光强度及Iba-1、iNOS蛋白表达水平均增加,eNOS、sGCa蛋白表达水平降低(P<0.05);与NP组相比,纳布啡+NP组PWMT和PWTL均升高,IL-6、IL-1β水平、Iba-1荧光强度及Iba-1、iNOS蛋白表达水平均降低,eNOS、sGCa蛋白表达水平均升高(P<0.05);NO/cGMP信号通路抑制剂7-N1可逆转纳布啡对NP大鼠的改善作用(P<0.05)。结论纳布啡可能通过激活NO/cGMP信号通路来改善NP模型大鼠的痛觉敏化。
Objective To investigate the effects of nalbuphine on the pain sensitization and spinal nitric oxide-cyclic guanosine monophosphate(NO/cGMP)pathway in neuropathic pain(NP)model rats.Methods An NP rat model was established,and 30 successfully modeled rats were randomly grouped into a model(NP)group,a nalbuphine intervention model(nalbuphine+NP)group,and a nalbuphine+7-nitroindazole intervention model(nalbuphine+7-N1+NP)group,with 10 rats in each group.And another 10 rats with L5 transverse process exposed but without spinal nerve ligation were taken as sham surgery(Sham)group.After drug intervention,mechanical stimulation foot contraction test was applied to detect the mechanical hypersensitivity in rats.The paw contraction heat latency test was utilized to detect the paw withdrawal thermal latency(PWTL).Enzyme-linked immunosorbent assay(ELISA)method was applied to detect the expression levels of interleukin(IL)-6 and IL-1βin the spinal cord of rats.Immunofluorescence staining was applied to detect the expression of the small glial cell marker Iba-1 in the spinal dorsal horn.Western blot was applied to detect the expression levels of Iba-1 and proteins related to the NO/cGMP signaling pathway.Results Compared with the Sham group,the paw withdrawal mechanical threshold(PWMT)and PWTL of rats in the NP group were reduced,the levels of IL-6 and IL-1β,the fluorescence intensity of Iba-1,and the expression levels of Iba-1 and iNOS proteins increased,the expression levels of eNOS and sGCa proteins decreased(P<0.05).Compared with the NP group,the PWMT and PWTL of rats in the nalbuphine+NP group were increased,the levels of IL-6,IL-1β,the fluorescence intensity of Iba-1,and the expression levels of Iba-1 and iNOS proteins decreased,the expression levels of eNOS and sGCa proteins increased(P<0.05).The NO/cGMP signaling pathway inhibitor 7-N1 could reverse the improvement effect of nalbuphine on NP rats(P<0.05).Conclusion Nalbuphine may improve pain sensitization in NP model rats by activating the NO/cGMP signaling pathway.
作者
高彦东
边步荣
韩利锋
Gao Yandong;Bian Burong;Han Lifeng(Department of Surgical Anesthesiology,The First Hospital of Yulin·The Second Affiliated Hospital of Yan'an University,Yulin 719000,China)
出处
《成都医学院学报》
2025年第5期730-734,共5页
Journal of Chengdu Medical College
基金
陕西省科学技术厅自然科学基础研究计划项目(No:2019JQ-983)。
