摘要
目的研究绿原酸(chorogenic acid,CGA)对完全弗氏佐剂(complete Freund’s adjuvant,CFA)所诱发的慢性疼痛症状的影响,并通过检测CGA对炎性小鼠脊髓背角AMPA受体突触表达的影响,探讨其作用机制。方法小鼠后足底皮下注射CFA,以诱导机械性痛觉超敏和热痛觉过敏;鞘内给予CGA,实时测定机械性缩足阈值(PWT)及热刺激潜伏期(PWL)的变化;分离脊髓背角,应用免疫印迹法检测AMPA受体亚基GluA1、GluA2的突触表达和磷酸化水平。结果鞘内注射CGA可剂量依赖性地提高疼痛小鼠的PWT和PWL;高剂量(200 ng)CGA对正常小鼠基础痛阈、运动机能并未产生明显影响;中剂量(100 ng)CGA可有效逆转CFA所诱发的GluA1亚基的突触表达亢进,并明显降低炎性小鼠GluA1-Ser845的磷酸化水平,但未影响GluA1-Ser831的磷酸化。结论CGA可通过特异性逆转脊髓背角GluA1-Ser845的过磷酸化、降低GluA1的突触表达而产生镇痛效应。
Aim To investigate the effect of chlorogenic acid(CGA)on chronic inflammatory pain induced by complete Freund’s adjuvant(CFA)and to observe the influence of CGA on CFA-induced synaptic expression of AMAP receptor in spinal dorsal horn.Methods CFA was injected intraplantarly into the hindpaws of mice to induce mechanical allodynia and thermal hyperalgesia.The changes of paw withdrawal threshold(PWT)and the paw withdrawal latency(PWL)were tested after intrathecal administration of CGA.Meanwhile,the synaptic expression and phosphorylation of AMPA receptor subunit were assessed by immunoblotting.Results The intrathecal injection of CGA produced dose-depended improvement of both PWT and PWL in CFA injected mice.A higher dose of CGA(200ng)did not influence the base thresholds of normal mice.The median dose of CGA(100 ng)effectively reversed the CFA-induced synaptic expression of GluA1;meanwhile,it suppressed the phosphorylation of GluA1 at Ser845,with no influence on phosphorylation at Ser831.Conclusions CGA might exert its analgesic effect by specifically inhibiting the phosphorylation of GluA1-Ser845 and the synaptic incorporation of GluA1-containing AMPA receptor.
作者
李银霞
高敏
白雪
刘燕妮
张亦涵
索占伟
LI Yin-xia;GAO Ming;BAI Xue;LIU Yan-ni;ZHANG Yi-han;SUO Zhan-wei(Dept of Molecular Pharmacology,School of Pharmacy,Lanzhou University,Lanzhou 730000,China)
出处
《中国药理学通报》
CSCD
北大核心
2021年第9期1251-1256,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 82073822)。
