摘要
目的探讨环磷酸腺苷(cAMP)/蛋白激酶A(PKA)信号通路在多西他赛(DTX)化疗所致大鼠神经病理性疼痛中的作用。方法经尾静脉注射DTX构建化疗所致神经病理性疼痛大鼠模型,采用PKA抑制剂H⁃89和PKA激动剂SP⁃CAMP进行干预。行为学试验测定大鼠机械缩足反射阈值(MWT)和热缩足反射潜伏期(TWL);ELISA法检测背根神经节中cAMP含量以及脊髓组织中炎性因子IL⁃1β、IL⁃6和TNF⁃α水平;免疫荧光法观察大鼠脊髓组织中星形胶质细胞活化标志物胶质纤维酸性蛋白(GFAP)表达情况;Western blot检测大鼠背根神经节中cAMP/PKA信号通路相关蛋白表达。结果H⁃89干预可显著提高模型大鼠MWT和TWL值(P<0.05),降低磷酸化环磷酸腺苷效应元件结合蛋白(p⁃CREB)和PKAc蛋白表达水平以及IL⁃1β、IL⁃6和TNF⁃α水平和GFAP平均荧光强度(P<0.05),而SP⁃CAMP干预则出现相反的效果,但均对背根神经节中cAMP含量无显著影响(P>0.05)。结论抑制cAMP/PKA信号通路可改善DTX化疗所致神经病理性疼痛,其机制可能与抑制星形胶质细胞活化、减少炎症因子释放有关。
Objective To investigate the role of cAMP/PKA signaling pathway in docetaxel(DTX)⁃induced neuropathic pain.Methods The rat model of chemotherapy⁃induced neuropathic pain was constructed by injecting DTX via tail vein,and PKA inhibitor H⁃89 and PKA agonist SP⁃CAMP were used for intervention.The mechanical withdrawal threshold(MWT)and thermal withdrawal latency(MWT)were measured by behavioral test.The content of cAMP in dorsal root ganglion and the level of IL⁃1β,IL⁃6 and TNF⁃αin spinal cord was detected by ELISA.The expression of astrocyte activation marker GFAP in rat spinal cord was observed by Immunofluores⁃cence.The protein expression of cAMP/PKA signaling pathway was detected by Western blot.Results Intervention with H⁃89 significantly increased the value of MWT and TWL in model rats(P<0.05),but decreased the protein expression level of phospho⁃cAMP⁃response element binding protein(p⁃CREB)and PKAc,as well as the level of IL⁃1β,IL⁃6 and TNF⁃αand the mean fluorescence intensity of GFAP(P<0.05),while SP⁃CAMP intervention showed the opposite effect,but both had no significant effect on the content of cAMP in the dorsal root ganglia(P>0.05).Conclusions Inhibition of cAMP/PKA signaling pathway can improve DTX⁃induced neuropathic pain in rats,and the mechanism may be related to inhibition of astrocyte activation and the reduction of inflammatory factor release.
作者
邓淑文
杨艳
夏红星
DENG Shuwen;YANG Yan;XIA Hongxing(The Affiliated Nanhua Hospital,Department of Pain,Hengyang Medical school,University of South China,Hengyang 421002,China;不详)
出处
《实用医学杂志》
CAS
北大核心
2021年第16期2075-2079,共5页
The Journal of Practical Medicine
基金
衡阳市科技局指导性项目(编号:189)。
