马钱子总碱成分分析及治疗家兔膝关节软骨损伤的机制  

Maqianzi(Nux Vomica)Total Alkali Analysis and Treatment Mechanism of Knee Cartilage Injury in Rabbits

作　　者：王莉莉 翟阳 张帅国 邬楠 籍学伟 马挺 WANG Lili;ZHAI Yang;ZHANG Shuaiguo;WU Nan;JI Xuewei;MA Ting(Market Supervision and Inspection Institute of Mentougou District of Beijing,Beijing China 102300;Inner Mongolia Autonomous Region Institute for Drug Control/Key Laboratory of Chinese and Mongolian Medicine Standards Research of Inner Mongolia Autonomous Region,Hohhot Inner Mongolia China 010020;Haidian 19th Retired Cadres Recuperation Center of Garrison District of Beijing,Beijing China 100143)

机构地区：[1]北京市门头沟区市场监督管理检验检测所,北京102300 [2]内蒙古自治区药品检验研究院/内蒙古自治区中蒙药标准研究重点实验室,内蒙古呼和浩特010020 [3]北京卫戍区海淀第十九离职干部休养所,北京100143

出　　处：《中医学报》2024年第8期1761-1769,共9页Acta Chinese Medicine

摘　　要：目的:分析马钱子总碱的有效成分,观察马钱子总碱治疗家兔膝关节软骨损伤的作用机制。方法:采用醇提取-有机溶剂萃取法制备马钱子总碱。通过高效液相色谱法(HPLC)和液相色谱串联质谱(LC-MS/MS)技术分析马钱子总碱的有效成分。从36只家兔中随机选取6只作为假手术组,其余家兔建立膝关节软骨损伤模型。将造模成功的家兔随机分为模型组、马钱子总碱高剂量组(24 mg·kg^(-1))、中剂量组(12 mg·kg^(-1))、低剂量组(6 mg·kg^(-1))及氟比洛芬组(37.5 mg·kg^(-1)),每组6只,每天给药1次,连续2周。采用高频X射线机观察膝关节形态,根据家兔运动情况进行疼痛评分。HE染色观察膝关节软骨的病理形态,ELISA法检测关节冲洗液中白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、前列腺素E2(prostaglandin E2,PGE2)含量。结果:马钱子总碱的有效成分包括马钱子碱、士的宁、伪马钱子碱、马钱子碱氮氧化物、士的宁氮氧化物、依卡精及番木鳖次碱等。与假手术组比较,模型组家兔的膝关节X线K-L评分升高(P<0.01);与模型组比较,马钱子总碱低剂量、高剂量组及氟比洛芬组家兔的膝关节X线K-L评分降低(P<0.01)。与假手术组比较,模型组家兔的疼痛评分、膝关节软骨Pelletier评分升高(P<0.05);与模型组比较,马钱子总碱各个剂量组家兔的疼痛评分、膝关节软骨Pelletier评分降低(P<0.05)。HE染色显示,模型组家兔膝关节滑膜细胞增生,软骨层破坏。马钱子总碱各个剂量组和氟比洛芬组家兔膝关节软骨组织未见明显滑膜或软骨下骨病变。与假手术组比较,模型组家兔关节冲洗液中TNF-α、PGE2、IL-6含量升高(P<0.01);与模型组比较,马钱子总碱高剂量组家兔关节冲洗液中TNF-α、PGE2含量降低(P<0.05)。结论:马钱子总碱可能通过马钱子碱、士的宁等有效成分,调控膝关节炎症因子水平,从而发挥�Objective:To analyze the active components of total strychnine of Maqianzi(Nux vomica)and to observe the mechanism of it in treatment of knee cartilage injury in rabbits.Methods:Total alkali of Maqianzi(Nux vomica)was prepared by alcohol extraction-organic solvent extraction.The active components of total strychnine of Maqianzi(Nux vomica)were analyzed by high-performance liquid chromatography(HPLC)and liquid chromatography tandem mass spectrometry(LC-MS/MS).Among the 36 rabbits,6 rabbits were randomly selected as the sham operation group,and the remaining rabbits were established as a model of knee cartilage injury.The rabbits were randomly divided into model group,total strychnine of Maqianzi(Nux vomica)high-dose group(24 mg·kg^(-1)),medium-dose group(12 mg·kg^(-1)),low-dose group(6 mg·kg^(-1))and flurbiprofen group(37.5 mg·kg^(-1)),with 6 rabbits in each group,administered once a day for 2 weeks.A high-frequency X-ray machine was used to observe the shape of the knee joint,and the pain score was carried out according to the movement of the rabbit.The pathological morphology of knee cartilage was observed by HE staining,and the contents of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and prostaglandin E2(PGE2)were detected in the joint irrigation fluid by ELISA.Results:The active components of total strychnine of Maqianzi(Nux vomica)include vauqueline,strychnine,pseudo-strychnine,brucine nitrogen oxide,strychnine nitrogen oxides,icajine and vomicine,etc.Compared with the sham operation group,the knee X-ray score of rabbits in the model group was increased(P<0.01).Compared with the model group,the knee X-ray score of rabbits in the low-dose and high-dose total strychnine of Maqianzi(Nux vomica)groups and the flurbiprofen group was reduced(P<0.01).Compared with the sham operation group,the pain score and Pelletier score of knee cartilage in the model group increased(P<0.05).Compared with the model group,the pain score and Pelletier score of knee cartilage in each dose group of total strychnine of Maqia

关 键 词：马钱子 马钱子总碱 膝关节软骨损伤 HPLC LC-MS/MS 炎症 家兔 

分 类 号：R285.5[医药卫生—中药学]