摘要
目的观察海马区微量注射血小板活化因子(PAF)受体拮抗剂银杏内酯B(BN52021)对坐骨神经分支选择性神经损伤(SNI)大鼠机械缩爪阈值以及海马PAF合酶LPCAT2和促炎细胞因子(TNF-α、IL-1β)表达的影响。方法选择海马区置管的雄性SD大鼠40只,随机分为4组(n=10):假手术组(Sham组)、模型手术组(SNI组)、BN52021治疗组、羟丙基-β-环糊精(HBC)对照组;海马区置管术后1周建立SNI疼痛模型,SNI手术后1d行海马区微量药物注射:BN52021治疗组给予银杏内酯B 10μg(1μL),HBC对照组给予HBC溶液1μL。SNI手术前1d和手术后1、7、14d检测大鼠机械缩爪阈值,第15天处死大鼠并取新鲜海马组织冻存,ELISA法检测海马TNF-α、IL-1β的表达,免疫荧光法检测LPCAT2的表达。结果 SNI组大鼠机械缩爪阈值明显降低(P<0.05),ELISA法检测海马TNF-α、IL-1β表达升高(均P<0.05),免疫荧光显示LPCAT2的表达增强(P<0.05);海马区微量注射银杏内酯B减轻大鼠触觉性异常痛敏,同时伴有海马区LPCAT2和TNF-α、IL-1β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大鼠的神经病理性疼痛,LPCAT2和促炎细胞因子TNF-α、IL-1β的表达下降可能与其镇痛机制有关。
Objective To investigate the effects of intrahippocampal microinjection with ginkgolide B on mechanical nociception threshold,expression of proinflammatory cytokine(TNF-αand IL-1β)and PAF synthase in hippocampus of rats with spared nerve injury(SNI).Methods Forty SD rats with cannula stereotaxically implanted into the dorsal hippocamus were randomly divided to 4 groups:sham operation group(Sham group),SNI model group(SNI group),BN52021 group and HBC vehicle control group(HBC group).SNI neuropathic pain model was established in all rats except sham groups a week after cannula implantation surgery.The rats in BN52021 group were administered with ginkgolide B 10μg(1μL)by intrahippocampal microinjection 1 day after SNI surgery,while the rats in HBC group were administered with 1μL 45% HBC.The behavior responses were observed 1 day before surgery and 1,7,and 14 days after surgery.The expression levels of TNF-αand IL-1βin hippocampus were detected by ELISA,and LPCAT2 in hippocampus were detected by immunofluorescence.Results Mechanical nociception threshold in SNI rats decreased significantly(P0.05),the expression levels of LPCAT2,TNF-αand IL-1βin hippocampus were significantly increased(all P0.05).Intrahippocampal microinjection with ginkgolide B depressed the expression of LPCAT2,TNF-αand IL-1βsignificantly(all P0.05),and attenuated the nociceptive response in SNI rats(P0.05).Conclusion Intrahippocampal microinjection with ginkgolide B may attenuate tactile allodynia in rats with SNI and depress the expression of LPCAT2,TNF-αand IL-1βin hippocampus.It suggests that down-regulation of LPCAT2,TNF-αand IL-1βexpression in hippocampus may be implicated in the antinociceptive mechanism in SNI rats administered with ginkgolide B by intrahippocampal microinjection.
作者
杨京利
张力
向勇
马国平
Yang Jingli;Zhang Li;Xiang Yong(Department of Anesthesiology,the Affiliated Shanghai Pudong Hospital of Fudan University,Shanghai 201399,China;Department of Pain Clinic,the Affiliated Taihe Hospital of Hubei Medical University,Shiyan 442000,China)
出处
《华中科技大学学报(医学版)》
CAS
CSCD
北大核心
2018年第4期427-430,共4页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基金
上海市浦东新区科技发展基金资助项目(No.PKJ2015-Y40)