如意珍宝片对骨关节炎性痛的抑制作用  

The inhibitory effect of Ruyizhenbao tablets on osteoarthritis pain

作　　者：陈海坤 柏虎虎 李宇哲 朱阅宾 葛安娜 吴树金 刘燕妮[1] 胡晓东[1] CHEN Hai-kun;BAI Hu-hu;LI Yu-zhe;ZHU Yue-bin;GE An-na;WU Shu-jin;LIU Yan-ni;HU Xiao-dong(Dept of Molecular Pharmacology,School of Pharmacy,Lanzhou University,Lanzhou 730000,China)

机构地区：[1]兰州大学药学院分子药理研究所,甘肃兰州730000

出　　处：《中国药理学通报》2022年第10期1579-1585,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81973296,32000703);兰州大学中央高校基本科研业务费专项资金资助(No lzujbky-2020-it27,lzujbky-2021-it37,lzujbky-2021-68)。

摘　　要：目的探讨如意珍宝片对骨关节炎性痛的作用及其机制。方法通过内侧半月板-胫骨韧带切断(destabilization of the medial meniscus,DMM),制作小鼠骨关节炎模型;灌胃给予不同剂量的如意珍宝片(12.5、25、50 mg·kg^(-1)),测定动态痛觉超敏和静态痛觉超敏;制备离体脊髓切片,膜片钳电生理学记录微小兴奋性突触后电流(miniature excitatory postsynaptic currents,mEPSCs)和微小抑制性突触后电流(miniature inhibitory postsynaptic currents,mIPSCs);免疫组织化学法观察脊髓背角NMDA受体(N-methyl-D-aspartate receptors)GluN1亚基第897位丝氨酸的磷酸化(pS897-GluN1)。结果如意珍宝片能够剂量依赖性地抑制DMM诱发的静态痛觉超敏及动态痛觉超敏,降低mEPSCs的频率,抑制pS897-GluN1的磷酸化,但对mIPSCs无明显影响。结论如意珍宝片能够降低突触前膜对兴奋性递质谷氨酸的释放,抑制脊髓背角NMDA受体的磷酸化,有效缓解骨关节炎性痛。Aim To investigate whether and how Ruyizhenbao tablets regulated osteoarthritis pain.Methods We transected the meniscotibial ligament of mice,which caused osteoarthritis by destabilizing the medial meniscus(DMM).Different doses of Ruyizhenbao tablets(12.5,25,50 mg·kg^(-1))were administered intragastrically.Dynamic and static mechanical allodynia were measured.The spinal cord slices were prepared to record miniature excitatory postsynaptic currents(mEPSCs)and miniature inhibitory postsynaptic currents(mIPSCs)by using patch clamp electrophysiological recordings.The phosphorylation of NMDA receptor(N-methyl-D-aspartate receptors)GluN1 subunit at S897 residue(pS897-GluN1)was observed by immunohistochemistry.Results Ruyizhenbao tablets dose-dependently attenuated the dynamic and static mechanical allodynia induced by DMM,reduced the frequency of mEPSCs and inhibited the pS897-GluN1 level.Ruyizhenbao tablets had no effects on mIPSCs.Conclusions Ruyizhenbao tablets effectively alleviate osteoarthritis pain by blocking the presynaptic release of excitatory transmitter glutamate and inhibiting the phosphorylation of NMDA receptor in spinal cord dorsal horn.

关 键 词：骨关节炎性痛 如意珍宝片 脊髓背角 痛觉超敏 DMM 磷酸化 

分 类 号：R-332[医药卫生] R282.71R322.81R392.11R441.1R684.3