抑制脊髓NMDAR⁃cADPR⁃RyRs信号通路减弱瑞芬太尼诱发的大鼠术后痛觉过敏  

Remifentanil-induced postoperative hyperalgesia is attenuated by inhibition of NMDAR-cADPR-RyRs signaling pathway in the spinal cord of rats

作　　者：钱玥 王芳[1] 张兢 夏天娇[2] 顾小萍[1] QIAN Yue;WANG Fang;ZHANG Jing;XIA Tianjiao;GU Xiaoping(Department of Anesthesiology,Nanjing Drum Tower Clinical College of Nanjing Medical University,Nanjing 210008;Medical School of Nanjing University,Nanjing 210008,China)

机构地区：[1]南京医科大学附属鼓楼临床医学院麻醉科,江苏南京210008 [2]南京大学医学院,江苏南京210008

出　　处：《基础医学与临床》2023年第9期1335-1340,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(81701371,81730033);江苏省自然科学基金(BK20170654)。

摘　　要：目的探讨NMDAR-cADPR-RyRs信号通路在瑞芬太尼诱发的大鼠痛觉过敏中的作用。方法建立瑞芬太尼诱发(术后)痛觉过敏(RIH)大鼠模型。将大鼠按随机数字表法分为6组(n=8):对照组、手术组、痛觉过敏(RIH)组、0.9%氯化钠溶液组、氯胺酮组和环状二磷酸腺苷核糖(cADPR)拮抗剂组。在术前和术后第1、2、3天检测机械缩足阈值(PWMT)和热缩足潜伏期(PWTL)阈值。Western blot检测脊髓背角神经元中p-NR2B、p-CaMKII和RyR1和RyR3的蛋白水平;酶循环法测量cADPR浓度。结果与手术组相比,RIH组在输注瑞芬太尼后第1和第2天PWMT和PWTL显著降低,同时脊髓背角p-NR2B、p-CaMKII、RyR1、RyR3和cADPR水平显著上调(P<0.05)。鞘内注射氯胺酮或8-Br-cADPR后,与RIH组相比RIH+Ketamin组和RIH+cADPR组的机械痛觉和热痛觉过敏缓解,p-NR2B、p-CaMKII、RyR1、RyR3和cADPR的表达水平下降(P<0.05)。结论抑制NMDAR-cADPR-RyRs信号通路可缓解瑞芬太尼诱发的大鼠术后痛觉过敏。Objective To investigate the role of NMDAR-cADPR-RyRs signaling pathway in remifentanil-induced hyperalgesia(RIH).Methods The rat model of postoperative hyperalgesia induced by remifentanil was established.SD rats were randomly divided into 6 groups as:control group,model group,RIH group,RIH+saline group,RIH+ketamine group and RIH+8-Br-cADPR group with 6 animals in each.N-methy-D-aspartic acid receptor(NMDA)antagonist ketamine or cyclic ADP-ribose(cADPR)antagonist 8-Br-cADPR was injected intrathecally 30 minutes before surgical operation in group RIH+ketamine and group RIH+8-Br-cADPR respectively.PWMT and PWTL were measured before operation and on the 1st,2nd and 3rd days after operation.Western blot was used to detect the protein level of p-NR2B,p-CaMKII,RyR1 and RyR3 in spinal dorsal horn neurons.The concentration of cADPR was measured by enzyme cycling assay.Results Compared with model group,PWMT and PWTL in RIH group decreased significantly on the first and the second day after remifentanil infusion,while p-NR2B,p-CaMKII,RyR1,RyR3 and cADPR in the spinal dorsal horn increased significantly(P<0.05).After intrathecal injection of ketamine or 8-Br-cADPR,hypersensitivity to mechanical pain and thermal pain was alleviated in RIH+ketamine group and RIH+8-Br-cADPR group,and the expression level of p-NR2B,p-CaMKII,RyR1,RyR3 and cADPR decreased as compared with RIH group(P<0.05).Conclusions Remifentanil-induced postoperative hyperalgesia of rat is attenuated by blocking NMDAR-cADPR-RyRs signaling pathway.

关 键 词：瑞芬太尼 痛觉过敏 氯胺酮 8-溴-环二磷酸腺苷核糖 兰尼碱受体 

分 类 号：R614[医药卫生—麻醉学]