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秋水仙碱缓释微丸对痛风性关节炎急性发作的预防作用研究 被引量:13

Preventive effect of colchicine sustained-release pellets on acute attack of gouty arthritis
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摘要 目的:探讨自制秋水仙碱缓释微丸对痛风性关节炎急性发作模型大鼠的预防作用。方法:采用流化床包衣技术制备秋水仙碱缓释微丸。将24只SD大鼠随机分为正常组、模型组、片剂组和缓释微丸组,每组6只。片剂组将秋水仙碱片研磨成粉,水溶后灌胃给药,缓释微丸组通过特制的灌胃器给予秋水仙碱缓释微丸,正常组和模型组给予等量生理盐水。给药14 d后,除正常组外,其他各组用尿酸钠诱导大鼠痛风性关节炎发作。比较各组大鼠踝关节肿胀度,酶联免疫吸附试验(ELISA)法检测大鼠血清中白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-α水平,苏木精—伊红(HE)染色观察大鼠踝关节炎性病变。通过比较各组大鼠腹泻率、摄食量、体重变化及血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、肌酐(Cr)含量来评估药物的安全性。结果:体外溶出结果显示,缓释微丸中的秋水仙碱成分在6 h内溶出80%以上,具有良好的缓释特性。与模型组比较,片剂组和缓释微丸组大鼠关节肿胀度及血清中IL-1β、TNF-α水平显著下降(P<0.05),踝关节滑膜增生及炎性浸润细胞明显减少。与片剂组比较,缓释微丸组大鼠关节肿胀度及IL-1β和TNF-α水平明显降低,摄食量和体重增加(均P<0.05),炎性细胞减少,两组肝、肾功能(AST、ALT、Cr含量)及腹泻率比较无明显差异(均P>0.05)。结论:相较于秋水仙碱市售普通片剂,所制缓释微丸对尿酸钠诱导的痛风性关节炎大鼠关节肿胀和炎症的抑制作用更显著,且安全性好。 Objective:To investigate the preventive effects of self-made colchicine sustained-release pellets on acute attack of gouty arthritis rats.Methods:Colchicine sustained-release pellets were prepared by fludized bed coating technology.Twenty-four SD rats were randomly divided into normal group,model group,tablet group and sustained-release pellet group,with 6 rats in each group.Colchicine tablets were ground into powder,dissolved in water and administered by gavage.Sustained-release pellet was administered through a special gavage.The normal group and model group rats were given the same amount of normal saline.After 14 days of administration,rat models of acute attack of gouty arthritis were established by using sodium urate except for the normal group.The swelling degree of ankle joint in each group was comares.The levels of interleukin(IL)-1βand tumor necrosis factor(TNF)-αin serum were detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylineosin(HE)staining was used to observe the pathological conditions of ankle inflammation.The safety of the drug was evaluated by comparing diarrhea rate,food intake,weight change and serum alanine aminotransferase(ALT),aspartate aminotransferase(AST)and creatinine(Cr)contents.Results:In vitro dissolution experiment showed that the colchicine sustained-release pellets dissolved more than 80%within 6 h,and it had a good sustained-release characteristic.Compared with the model group,the joint swelling degree,serum IL-1βand TNF-αlevels(P<0.05),and the proliferation and infiltrating cells of ankle synovium were decreased significantly in tablet group and sustained-release pellet group.Compared with tablet group,joint swelling,inflammatory cells and the serum levels of IL-1βand TNF-αin sustained-release pellet group were significantly decreased,while food intake and body weight were increased(P<0.05).The liver and kidney function(AST,ALT,and Cr contents)and diarrhea rate were not significantly different between the two groups(P>0.05).Conclusion:Compared with the common colchicine tablets sold in markets,the prepared sustained-release pellets have more obvious effect on relieving joint swelling and inflammatory symptoms in rats with gouty arthritis induced by sodium urate,and it is safe.
作者 韦业娟 吕白 雷雅然 杨国宝 丁雅宁 王玉丽 高春生 焦杨 Wei Yejuan;Lyu Bai;Lei Yaran;Yang Guobao;Ding Yaning;Wang Yuli;Gao Chunsheng;Jiao Yang(School of Pharmacy,Guangxi Medical University,Nanning 530000,China;Institute of Toxicology and Pharmacology,Academy of Military Medical Sciences,Beijing 100850,China;School of Pharmacy,Qiqihar Medical University,Qiqihar 161006,China;School of Pharmaceutical Engineering,Shenyang Pharmaceutical University,Shenyang 117004,China)
出处 《广西医科大学学报》 CAS 2022年第1期21-27,共7页 Journal of Guangxi Medical University
基金 国家“重大新药创制”科技重大专项资助项目(No.2018ZX09711003-008-001) 广西自然科学基金面上项目(No.2018GXNSFAA281217)。
关键词 秋水仙碱 缓释微丸 痛风性关节炎 colchicine sustained release pellets gouty arthritis
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