雷公藤多苷纳米粒的制备及其对关节炎大鼠的治疗作用  

Preparation of tripterygium glycoside nanoparticles andtherapeutic effect on arthritis rats

作　　者：王志荣 李嫚 张振强[1] 闫敏[1] 武香香[1] 曾华辉[1] WANG Zhi-rong;LI Man;ZHANG Zhen-qiang;YAN Min;WU Xiang-xiang;ZENG Hua-hui(College of Chinese Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学中医药科学院,河南郑州450046

出　　处：《中国药理学通报》2024年第1期125-132,共8页Chinese Pharmacological Bulletin

基　　金：河南省科技研发计划联合基金(优势学科培育类)-培育项目(No 222301420060);河南省自然基金面上项目(No 222300420482);河南省优秀青年基金资助项目(No 212300410057)。

摘　　要：目的 制备雷公藤多苷纳米粒,探究其对胶原诱导型(collagen-induced arthritis, CIA)关节炎大鼠的治疗作用。方法 运用薄膜分散法制备雷公藤多苷纳米粒,对其进行质量评估。构建CIA模型,进行药物干预,称量大鼠体质量、测定足趾肿胀度和关节炎指数;观察大鼠脏器、膝、踝关节滑膜的病理改变;检测大鼠血清中肝肾功能水平和炎症因子表达。结果 制备的雷公藤多苷纳米粒在电镜下呈圆粒状且分布均匀,性质稳定。相较于模型组,给药组大鼠左右足趾肿胀度均明显下降(P<0.01),关节炎指数明显降低(P<0.01)。其中TG-NPs组的疗效优于TG组。与正常组相比,大鼠心脏、脾、肾、睾丸指数均明显降低(P<0.05,P<0.01)。TG-NPs组膝踝关节软骨病理损伤明显减轻,凋亡的滑膜细胞增加;与模型组相比,TG-NPs组大鼠血清中的ALT、BUN、CRE水平均明显降低(P<0.05),IL-1β、TNF-α和IL-6含量下降明显(P<0.05)。结论 TG-NPs通过诱导滑膜细胞凋亡和降低炎性细胞因子的表达对CIA有较好的治疗作用,通过静脉注射血液循环,可实现药物的缓、控释,避免口服药物造成的首过效应,减轻脏器的毒性,为治疗类风湿关节炎的新型纳米制剂的开发提供了实验依据。Aim To prepare tripterygium glycoside nanoparticles and probe into their therapeutic effect on collagen-induced arthritis(CIA)rats.Methods Tripterygium glycosides polyglycoside nanoparticles were prepared by thin film dispersion method and their quality was assessed.The CIA model was established and drug intervention performed.The body weight,toe swelling degree and arthritis index were measured.The pathological changes of the organs,knee and ankle synovium were observed.The serum levels of kidney function and inflammatory cytokine expression were detected in rats.Results The prepared tripterygium wilfordii polyglycoside nanoparticles were round particles with uniform distribution and stable properties under electron microscope.Compared with the model group,the swelling of the left and right toes of medication group significantly decreased(P<0.01),and the arthritis index markedly decreased(P<0.01).Among them,the efficacy of the TG-NPs group was better than that of the TG group.Compared with the normal group,the indexes of heart,spleen,kidney and testis all significantly decreased(P<0.05,P<0.01).TG-NPs group had a significantly reduced pathological ankle-joint injury in knee cartilage and increased apoptotic synovial cells.Compared with the model group,the serum levels of ALT and BUN and CRE in TG-NPs group were significantly lower(P<0.05),and IL-1β,TNF-αand IL-6 levels decreased significantly(P<0.05).Conclusions TG-NPs have good therapeutic effect on CIA through induction of synovial cell apoptosis and decrease of the expression of inflammatory cytokines.By intravenous injection of blood circulation,slow and controlled release of drugs can be achieved,the first pass effect caused by oral drug can be avoided,the viscera toxicity can be reduced,which provides an experimental basis for the development of new nanoagents for the treatment of rheumatoid arthritis.

关 键 词：雷公藤多苷 纳米粒 新型给药系统 类风湿关节炎 CIA模型 炎症因子 毒性 

分 类 号：R-332[医药卫生] R284.1R364.5R593.22R944.9