首页|期刊导航|中国药物评价|复力捷改善碘乙酸钠引起大鼠骨关节炎及其早期安全性研究

复力捷改善碘乙酸钠引起大鼠骨关节炎及其早期安全性研究OA

Amelioration of Sodium Iodoacetate-Induced Osteoarthritis in Rats by Fulijie and Its Early Safety Evaluation

中文摘要英文摘要

目的:探索复力捷对碘乙酸钠引起的大鼠骨关节炎的改善作用及其早期安全性研究.方法:57只SD大鼠随机分为空白对照组、模型组、复力捷高、中、低剂量组(400、200、100 mg·kg-1)、塞来昔布组(80 mg·kg-1);以大鼠膝关节注射碘乙酸钠1 d后开始连续灌胃给药21 d.记录每只大鼠的体重变化,并检测其缩足阈值,H&E染色观察各组大鼠膝关节病理损伤并对病理切片进行Mankin评分;检测高剂量给药组大鼠的脏器系数,取血清测定脏器毒性指标变化,并检测膝关节组织中总超氧化物歧化酶(Superoxide dismutase,SOD)、丙二醛(Malondialdehyde,MDA)的含量;ELISA检测大鼠膝关节组织中肿瘤坏死因子α(TNF-α)的表达水平.结果:与模型组相比,复力捷高、中、低剂量组均能改善大鼠骨关节炎损伤,其中高剂量给药组的疗效显著,且优于阳性药塞来昔布;高剂量给药组能显著拮抗碘乙酸钠造模后引起的SOD活性下降及MDA含量的升高,并降低膝关节组织中TNF-α的表达水平;通过测量高剂量给药组各脏器系数、毒性指标结果发现,复力捷并无明显体内毒性.结论:复力捷可有效地改善碘乙酸钠引起的大鼠骨关节炎,其作用可能与抗炎抗氧化有关,且此药对大鼠无毒副作用,安全性良好.

Objective:To explore the therapeutic effects of Fulijie on sodium iodoacetate-induced osteoarthritis in rats and investigate its early safety profile.Methods:A total of 57 SD rats were randomly divided into the blank control group,model group,high,medium,and low-dose Fulijie groups(400,200,100 mg·kg-1),and a celecoxib group(80 mg·kg-1).After the rats' knee joints were injec-ted with sodium iodoacetate for one day,rats were treated with continuous oral administration for 21 days.Body weight changes were recorded,and the threshold of foot withdrawal was measured.The pathological damage of the knee in each group was observed by H&E staining,and the Mankin score for histopathological evaluation was applied.Organ coefficients were measured in the high-dose group,and serum levels of organ toxicity indicators were assessed.The levels of total superoxide dismutase(SOD)and malondialdehyde(MDA)in the knee tissue were measured,and the expression of tumor necrosis factor-α(TNF-α)in the knee tissue was detected by ELISA.Results:Compared to the model group,all Fulijie-treated groups(high,medium,and low doses)showed improvement in the osteoarthri-tis damage in rats,with the high-dose group demonstrating significantly better efficacy,even superior to approved drug celecoxib.The high-dose group notably reversed the decrease in SOD activity and the increase in MDA levels caused by sodium iodoacetate-induced osteo-arthritis model,while reducing the expression of TNF-α in knee tissue.Toxicity tests in the high-dose group,including organ coefficients and toxicity markers,revealed no significant changes,indicating no obvious toxicity.Conclusion:Fulijie effectively ameliorates sodium iodoacetate-induced osteoarthritis in rats,likely through anti-inflammatory and antioxidative mechanisms.Additionally,Fulijie shows no obvious toxic and side effects,indicating a favorable safety profile.

张佳敏;吴帅;王志宇;童海兵;庞涛

中国药科大学多靶标天然药物全国重点实验室,新药筛选与药效评价中心,江苏南京 210009杭州泽健医药科技有限公司,浙江 杭州 515044中国药科大学多靶标天然药物全国重点实验室,新药筛选与药效评价中心,江苏南京 210009杭州泽健医药科技有限公司,浙江 杭州 515044中国药科大学多靶标天然药物全国重点实验室,新药筛选与药效评价中心,江苏南京 210009

医药卫生

复力捷骨关节炎炎症因子氧化应激早期安全性

FulijieOsteoarthritisInflammatory factorsOxidative stressEarly safety

《中国药物评价》 2025 (3)

204-210,7

评论