海马区血小板活化因子合酶及其受体的表达对选择性神经损伤大鼠痛觉敏化的影响

摘要

目的 探讨海马区血小板活化因子(PAF)合酶(LPCAT1、LPCAT2)及其受体(PAFR)在大鼠坐骨神经分支选择性神经损伤(SNI)所致神经病理性疼痛中的作用.方法 选择海马区置管成功的雄性SD大鼠40只,随机分为4组(n=10):假手术组(Sham组),模型组(SNI组),模型+银杏内酯B组(SNI+BN52021组)和溶剂对照组(SNI+HBC组).SNI+BN52021组在SNI手术后2 d通过海马区微量注射给予银杏内酯B 10 μg(溶解于1 μL的HBC溶液),SNI+HBC组则给予1 μL的HBC溶液.分别于术前1 d和术后1、3、5、7、10、14 d记录各组动物的机械缩爪阈值(PWMT)和辐射热缩爪潜伏期(PWTL);第15天取大鼠新鲜海马组织,RT-PCR检测LPCAT1、LPCAT2以及PAFR的表达.结果 SNI大鼠PWMT值术后第1天开始明显降低(P<0.05),海马组织中LPCAT2及PAFR的表达增强(均P<0.05),LPCAT1的表达变化不明显(P>0.05);海马区微量注射BN52021组大鼠的PWMT值升高,海马组织中LPCAT2及PAFR的表达下降(均P<0.05).结论 海马区微量注射银杏内酯B可减轻SNI大鼠的机械性痛敏,抑制海马区LPCAT2和PAFR的表达,海马区PAF/PAFR信号通路可能参与了SNI大鼠神经病理性疼痛机制.%Objective To investigate the roles of platelet-activating factor(PAF)synthases(LPCAT1 and LPCAT2)and its receptor(PAFR)in neuropathic pain induced by spared nerve injury(SNI)in hippocampus.Methods Totally,40 SD rats with the cannula stereotaxically implanted into the dorsal hippocamus were randomly divided into 4 groups:Sham group,SNI group,Ginkgolide B group(SNI+BN52021 group)and vehicle control group(SNI+HBC group).The rats in SNI+BN52021 group were administered by intrahippocampal injection with Ginkgolide B 10 μg/μL 2 days after SNI surgery,and the rats in SNI+HBC group were administered by intrahippocampal injection with 45% HBC 1 μL.The paw withdrawal mechanical threshold(PWMT)and paw withdrawal thermal latency(PWTL)were recorded 1 day before surgery and 1,3,5,7,10 and 14 days after surgery.The expression of PAF synthases(LPCAT1 and 2)and PAF receptor(PAFR)in hippocampus were detected by RT-PCR.Results PWMT decreased significantly 1 day after surgery in SNI group(P<0.05).The expression levels of LPCAT2 and PAFR were increased significantly in hippocampus in SNI group(P<0.05).PWMT increased significantly in SNI rats administered by intrahippocampal injection with Ginkgolide B(P<0.05),and the expression of LPCAT2 and PAFR decreased significantly in hippocampus in SNI+BN52021 group(P<0.05).Conclusion Intrahippocampal injection with Ginkgolide B could decrease the expression of LPCAT2 and PAFR,and alleviate mechanical hyperalgesia.It suggests that PAF/PAFR in hippocampus participates in the mechanism of neuropathic pain after SNI surgery.