复方南星止痛膏2种给药间隔抗类风湿关节炎药效比较  

Comparative study of two different application intervals of Compound Nanxing Zhitong Plaster on collagen⁃induced arthritis rats

作　　者：李志强[1,2] 商晶 范小雪[1,2] 刘婧 曹亮 王振中 张新庄[1,2] 肖伟 LI Zhi-qiang;SHANG Jing;FAN Xiao-xue;LIU Jing;CAO Liang;WANG Zhen-zhong;ZHANG Xin-zhuang;XIAO Wei(Jiangsu Kangyuan Pharmaceutical Co.,Ltd.,Lianyungang 222000,China;National Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture,Lianyungang 222001,China)

机构地区：[1]江苏康缘药业股份有限公司,连云港222000 [2]中药制药过程控制与智能制造技术全国重点实验室,连云港222001

出　　处：《中国新药杂志》2024年第17期1796-1804,共9页Chinese Journal of New Drugs

摘　　要：目的:建立胶原诱导关节炎(collagen-induced arthritis,CIA)大鼠模型,比较复方南星止痛膏不同给药间隔的药效变化。方法:30只大鼠分为空白组、模型对照组、复方南星止痛膏贴24 h隔日1贴治疗组、复方南星止痛膏每日贴8 h治疗组、双氯芬酸钠贴片阳性对照组,每组6只。分组后d 1开始给药,连续给药3周。每周进行关节炎评分、足趾肿胀度和机械刺激缩足反应阈值检测,实验终点Elisa检测血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-17(interleukin-17,IL-17)、降钙素基因相关肽(calcitonin gene-related peptide,CGRP)含量,HE染色进行大鼠踝关节病理组织观察和评分。结果:与模型对照组比较,复方南星止痛膏每日贴24 h隔日1贴治疗组和每日贴8 h治疗组均能显著降低CIA大鼠的关节炎评分和足趾肿胀度(P<0.05,P<0.01);2种给药间隔均从给药第2周开始显著提高CIA大鼠的机械刺激缩足反应阈值(P<0.001);每日贴8 h治疗组能显著降低CIA大鼠踝关节组织病理评分(P<0.05),每日贴24 h隔日贴治疗组对CIA大鼠踝关节组织病理评分均有降低的趋势,但无统计学差异(P>0.05);2种给药间隔均能显著降低血清TNF-α,IL-17,CGRP水平(P<0.05,P<0.01)。结论:复方南星止痛膏2种给药间隔治疗连续用药3周后对CIA大鼠在抗炎、镇痛方面的治疗作用相当,且每日贴8 h治疗组对大鼠踝关节组织病理方面的改善作用要优于每日贴24 h隔日1贴治疗组。Objective:To compare the efficacy of two different dosing intervals of Compound Nanxing Zhitong Plaster(FFNX)in the treatment of collagen⁃induced arthritis(CIA)rats model.Methods:A total of 30 rats were divided into 5 groups with 6 rats in each group according to arthritis score.The groups are normal group,model group,Compound Nanxing Zhitong Plaster group(applied for 24 h and every other day),Compound Nanxing Zhitong Plaster group(applied for 8 h),and diclofenac sodium patch group.The drug was applied on the first day after grouping and continued for three weeks.Arthritis score,percentage of toe swelling and threshold value of mechanical stimulation of foot withdrawal response were measured weekly.The levels of IL⁃17,TNF⁃αand CGRP in serum of rats were detected by Elisa.The pathological changes of ankle joints were observed by hematoxylin eosin(HE)staining,and the degree of pathological injury was scored.Results:Compared with the model group,the arthritis score and percentage of toe swelling of CIA rats were significantly decreased in both 24 h gourp and 8 h group(P<0.05,P<0.01).The threshold of mechanically stimulated foot withdrawal response in CIA rats was significantly increased by the two different dosing intervals from the second week(P<0.001).The group applied 8 hours a day could significantly reduce the histopathological score of ankle joint in CIA rats(P<0.05),and the group applied 24 h once every other day showed a decrease in the histopathological score of ankle joints in CIA rats with no significant difference(P>0.05).The levels of TNF⁃αand IL⁃17 in serum were significantly decreased by the two different dosing intervals(P<0.05,P<0.01).Conclusion:Two different dosing intervals of CNZP showed similar anti⁃inflammatory and analgesic effects on CIA rats after three weeks of continuous application.Specifically,the therapeutic effects on the improvement of ankle joint histopathology in the treatment group of 8 h every day were better than those in the treatment group of 24 h every other day.

关 键 词：复方南星止痛膏 类风湿关节炎 胶原诱导关节炎大鼠 抗炎 镇痛 

分 类 号：R965[医药卫生—药理学]