淫羊藿素联合吗啡对骨癌痛小鼠的镇痛效应研究
Study on the analgesic effects of icaritin in combination with morphine on bone cancer pain in mice
杨雪伟 1袁贤达 2田越 3孙琳琳 3蔡捷 3孟坤 2邢国刚3
作者信息
- 1. 北京大学神经科学研究所,北京大学基础医学院神经生物学系,教育部/卫健委神经科学重点实验室,北京 100191;北京大学第一医院内分泌科,北京 100034
- 2. 北京盛诺基医药科技股份有限公司,北京 102206
- 3. 北京大学神经科学研究所,北京大学基础医学院神经生物学系,教育部/卫健委神经科学重点实验室,北京 100191
- 折叠
摘要
目的:探究淫羊藿素对骨癌痛(bone cancer pain,BCP)小鼠的镇痛效应,以及淫羊藿素与吗啡联合用药的镇痛效应;确定半效剂量淫羊藿素与吗啡联合用药,在达到吗啡最大镇痛效应时所减少的吗啡用量.方法:使用雄性 C57BL/6J 小鼠及路易斯(Lewis)肺癌细胞建立 BCP小鼠模型.通过测定机械刺激缩足反射阈值(mechanical withdrawal threshold,MWT),冷刺激缩足潜伏期(paw withdrawal latency,PWL)以及自发抬足次数和抬足保护时间以评估小鼠疼痛敏感度.结果:自造模后第7～14天起,BCP小鼠左侧(荷瘤侧)后爪MWT和PWL明显降低,自发抬足次数和抬足保护时间明显上升,并持续存在(P<0.05).造模后第7～14天给予淫羊藿素,自第10～14天起淫羊藿素明显增加BCP小鼠左侧后爪的MWT和PWL,并减少自发抬足次数和抬足保护时间,停药后效应持续至造模后第18天(即停药后第4天)(P<0.05).应用2倍EC50 剂量淫羊藿素(200 mg/kg)与吗啡联合用药可明显延长停药后镇痛效应,停药后镇痛效应持续至造模后第21天(即停药后第7天)(P<0.05).应用半效剂量淫羊藿素(100 mg/kg)与吗啡联合用药,达到吗啡最佳镇痛效应时最多可减少60%吗啡用量.结论:淫羊藿素对BCP小鼠有明显的镇痛效应,当与吗啡联合用药时,不仅明显延长了停药后的镇痛效应,还能够减少高达60%的吗啡用量.
Abstract
Objective:This study aimed to investigate the analgesic effect of icaritin on bone cancer pain(BCP)in mice and the potential synergistic analgesic effect of icaritin and morphine.Additionally,we sought to determine the extent of morphine dose reduction when icaritin was administered at a half-effective dose in combination with morphine.Methods:We established a mouse model of BCP using male C57BL/6J mice and lewis lung carcinoma(LLC)cells.We assessed the pain threshold by measuring the mechanical withdrawal threshold(MWT)in response to mechanical stimulation,the paw withdrawal latency(PWL)in response to cold stimulation,the frequency of spontaneous flinches,and the time spent guarding.Results:Between the 7th and 14th days after modeling,BCP mice exhibited a significant decrease in MWT and PWL in the ipsilateral(tumor-bearing)hind paw,along with a significant increase in spontaneous flinches and time spent guarding(P<0.05).Icaritin was administered from the 7th to the 14th day after modeling.Starting from the 10th to the 14th day,icaritin significantly increased MWT and PWL in the ipsilateral hind paw of BCP model mice,while reduced the frequency of spontaneous flinches and the time spent guarding.These analgesic effects persisted until the 18th day after surgery(i.e.,the 4th day after drug discontinuation)(P<0.05).When icaritin was administered at a dose of 2×EC50(200 mg/kg)in combination with morphine,it significantly prolonged the post-analgesic effects after drug discontinuation,with these effects lasting until the 21st day after surgery(i.e.,the 7th day after drug discontinuation)(P<0.05).Furthermore,when icaritin was administered at a half-effective dose(100 mg/kg)in combination with morphine,it reduced the required morphine dosage by up to 60%while maintaining the best analgesic effect achievable with morphine.Conclusion:Icaritin exhibits a significant analgesic effect on bone cancer pain in mice.When combined with morphine,icaritin not only prolongs post-analgesic effects after drug discontinuation but also reduces the required morphine dosage by up to 60%.
关键词
骨癌痛/淫羊藿素/吗啡/镇痛效应Key words
bone cancer pain/icaritin/morphine/analgesic effect引用本文复制引用
基金项目
国家自然科学基金(82371227)
国家自然科学基金(82171226)
国家自然科学基金(81974169)
国家自然科学基金(81671085)
北京市自然科学基金(7222105)
国家重点研发计划(2019YFC1712104)
北京大学医学部-英国伦敦国王学院联合医学研究所(JI)联合研究项目(BMU2021KCL001)
出版年
2024
NETL
NSTL
维普
万方数据