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雷公藤甲素联合硫酸软骨素脂质体对关节炎大鼠的治疗作用 被引量:7

Therapeutic effect of chondroitin sulfate combined with triptolide liposome on arthritic rats
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摘要 目的比较游离雷公藤甲素(triptolide,TP)、游离雷公藤甲素-硫酸软骨素(triptolide-chondroitin sulfate,TP-CS)、雷公藤甲素脂质体(TP-Lips)及雷公藤甲素联合硫酸软骨素脂质体(TP-CS-Lips)对胶原诱导的关节炎大鼠(CIA)的治疗作用。方法48只SPF级SD大鼠,随机选择8只作为Control组,其余40只注射完全弗氏佐剂-鸡II型胶原以建立CIA。将造模成功的40只大鼠再随机分为Model组、TP组、TP-CS组、TP-Lips组及TP-CS-Lips组。治疗组每天腹腔注射相应的药物(TP:30μg·kg^(-1),CS:100 mg·kg^(-1)),Control组和Model组大鼠腹腔注射相同体积的0.9%氯化钠溶液,每天1次,治疗周期为28 d。分别于给药前(0 d)、给药7 d、14 d、21 d及28 d对大鼠进行体质量称定、关节炎指数评定;分析各组大鼠胸腺指数与脾指数;HE染色观察各组大鼠膝关节软骨病理改变;ELISA检测大鼠血清中炎症因子IL-1β、TNF-α及IL-6表达情况。结果与Model组相比,TP-CS-Lips使关节炎大鼠体质量增加(P<0.05),关节炎指数评分降低(P<0.05);大鼠胸腺和脾指数降低(P<0.05);膝关节软骨病理损伤显著减轻;血清中IL-1β、TNF-α及IL-6水平下降(P<0.05)。且TP-CS-Lips对关节炎大鼠的治疗作用优于TP、TP-CS及TP-Lips。结论TP-CS-Lips能够明显增强对CIA的治疗作用,为其开发成为治疗类风湿关节炎的纳米制剂提供了实验依据。 Aim To compare the therapeutic effects of free triptolide(TP),free triptolide-chondroitin sulfate(TP-CS-Lips),triptolide liposome(TP-Lips)and triptolide combined with chondroitin sulfate liposome(TP-CS-Lips)on collagen-induced arthritis(CIA)rats.Methods A total of 48 SD SPF rats were selected in the study,8 of which were randomly treated as controls and the remained 40 rats were injected with complete Frederik’s adjuvant-chicken type II collagen to establish CIA.The 48 rats successfully modeled were randomly divided into five groups:model group,TP group,TP-CS group,TP-Lips group and TP-CS-Lips group.The treatment groups were intraperitoneally injected with corresponding drugs(TP:30μg·kg^(-1),CS:100 mg·kg^(-1))every day,while the control group and model group were intraperitoneally injected with an equal volume of 0.9%sodium chloride solution once a day,with a treatment cycle of 28 days.Before administration(0 d)and at 7 d,14 d,21 d and 28 d,the body mass index and arthritis index of rats were evaluated;thymus index and splenic index of each group were analyzed.HE staining was used to observe the pathological changes of cartilage.The expressions of inflammatory cytokines IL-1,TNF-and IL-6 in serum were detected by ELISA.Results Compared with model group,TP-CS-Lips significantly increased the body mass of arthritic rats(P<0.05),and the arthritis index score was also significantly induced(P<0.05);thymus and spleen indexes of rats significantly decreased(P<0.05);pathological injury of cartilage of knee joint was significantly reduced;the IL-1,TNF-and IL-6 levels of serum also significantly decreased(P<0.05).Furthermore,the therapeutic effect of TP-CS-Lips was superior to that of TP,TP-CS and TP-Lips in arthritic rats.Conclusions TP-CS-Lips could significantly enhance the therapeutic effect of CIA,which provides experimental basis for the development of nano-agents for the treatment of arthritis.
作者 郭睿博 孔亮 张璐 蔡馥伊 李学涛 GUO Rui-bo;KONG Liang;ZHANG Lu;CAI Fu-yi;LI Xue-tao(School of Pharmacy, Liaoning University of TCM, Dalian Liaoning 116600, China)
出处 《中国药理学通报》 CAS CSCD 北大核心 2021年第7期991-996,共6页 Chinese Pharmacological Bulletin
基金 兴辽英才计划(No XLYC1807132)。
关键词 类风湿关节炎 雷公藤甲素 硫酸软骨素 脂质体 胶原诱导关节炎 炎症因子 rheumatoid arthritis triptolide chondroitin sulfate liposomes collagen-induced arthritis inflammatory cytokine
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