Notch信号通路在长春新碱诱导神经病理性疼痛中的作用  

THE ROLE OF SPINAL NOTCH SIGNALING PATHWAY IN THE DEVELOPMENT OF VINCRISTINE-INDUCED NEUROPATHIC PAIN IN RATS

作　　者：李余星 秦冰杰 刘小虎 谭潇[2] 郑军[2] 郑卫红[1] LI Yu-Xing;QIN Bing-Jie;LIU Xiao-Hu;TAN Xiao;ZHENG Jun;ZHENG Wei-Hong(College of Medical Science of China Three Gorges University,Third-grade Pharmacology Laboratory on Traditional Chinese Medicine Approved by State Administration of Traditional Chinese Medicine,Yichang 443002,China;The First College of Clinical Medical Science of China Three Gorges University,Institute of Hepatopancreatobilary Surgery,Yichang 443003,China;The First People' s Hospital Of Yidu,Pharmaceutical Preparation Section,Yichang 443300,China)

机构地区：[1]三峡大学医学院国家中药药理科研三级实验室,宜昌443002 [2]三峡大学第一临床医学院肝胆胰外科研究所,宜昌443003 [3]宜都市第一人民医院药剂科,宜昌443300

出　　处：《中国疼痛医学杂志》2019年第8期569-574,共6页Chinese Journal of Pain Medicine

基　　金：湖北省自然科学基金项目（2013CFC066）;宜昌市科学研究与开发项目（A13301-57）

摘　　要：目的:研究Notch信号通路在长春新碱(vincristine,VCR)诱导大鼠神经病理性疼痛中的作用。方法:大鼠鞘内置管并筛选出合格SD大鼠40只,采用随机区组的方法分为4组(n=10):对照组(control)、长春新碱致化疗痛模型组(VCR)、DAPT多次给药+VCR组(DAPT(8)+VCR)、DAPT单次给药+VCR组(DAPT(1)+VCR)。隔日腹腔注射长春新碱(125μg/kg)建立化疗痛模型,Notch信号通路抑制剂DAPT从建模前1d起鞘内注射(50μg/μl),其它各组注射生理盐水。测痛仪测定大鼠痛阈值;分子生物学技术检测脊髓背角NICD蛋白、Hes1mRNA表达。结果:与对照组比较,VCR组大鼠痛阈值显著降低(P<0.01),NICD、Hes1mRNA表达显著升高(P<0.01);与VCR组比较,DAPT多次给药+VCR组、DAPT单次给药+VCR组大鼠痛阈值均升高,NICD、Hes1mRNA表达显著降低(P<0.05orP<0.01)。结论:Notch信号通路的活化可能参与了长春新碱诱导的神经病理性疼痛的发生、发展;抑制其活化能有效缓解大鼠痛觉过敏反应。Objective:To explore the role of spinal Notch signaling pathway in the development of chemotherapy- induced neuropathic pain.Methods:Fourty Sprague-Dawley rats with intrathecal catheterization were selected and divided into 4 groups (n = 10):control group,Vincristine (VCR) group,repeated administration of DAPT (8)+ VCR group,single administration of DAPT(1)+ VCR group.Intraperitoneal injection of vincristine (125 μg/kg) every other day was used to establish the model of vincristine-induced neuropathic pain.DAPT (50 μg/μl,inhibitor of Notch signaling pathway) or physiological saline solution was administrated in each group from day 0 to day 7.Electronic von Frey,thermal radiation and cold anesthesiometer were used to measure paw withdrawl threshold of rats.The expression of NICD (Notch intracellular domain) and Hes1 mRNA in the spinal dorsal horn was detected.Results:Compared with the control group,the pain threshold decreased and the mRNA expression of NICD and Hes1 increased in VCR group (P < 0.01).Compared with the VCR group,the pain threshold increased and the expression of NICD and Hes1 decreased in DAPT + VCR groups (P < 0.05 or P < 0.01).Conclusion:Notch signaling pathway may be involved in the occurrence and development of neuropathic pain induced by vincristine.Inhibiting the activation of notch signaling pathway can efficiently alleviate hyperalgesia in rats.

关 键 词：长春新碱 NOTCH信号通路 化疗痛 DAPT 

分 类 号：R741[医药卫生—神经病学与精神病学]