伸筋草与甲氨蝶呤对类风湿性关节炎大鼠的疗效及肝毒性比较分析

Comparison of efficacy and hepatotoxicity about Lycopodii Herba and methotrexate in treatment of rheumatoid arthritis

目的比较伸筋草与甲氨蝶呤治疗大鼠类风湿性关节炎(RA)的疗效及安全性(肝毒性)。方法 40只雄性SD大鼠,随机分为对照组、模型组、甲氨蝶呤组及伸筋草高、低剂量组。采用牛II型胶原蛋白-不完全弗氏佐剂乳剂诱导复制RA大鼠模型,通过检测各组大鼠后足趾容积、血清中类风湿性因子(RF)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)水平,系统比较伸筋草与甲氨蝶呤治疗RA的疗效。通过检测各组大鼠血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(T-BIL)水平,评价伸筋草与甲氨蝶呤治疗RA时是否伴有肝毒性,对两者的安全性进行比较。结果与对照组相比,模型组大鼠后足趾容积、血清中RF、TNF-α、IL-1β水平均明显升高(P<0.01);与模型组相比,给予伸筋草高、低剂量和甲氨蝶呤后均可显著降低大鼠后足趾容积及血清中RF、TNF-α、IL-1β水平(P<0.05)。与对照组相比,模型组大鼠血清中ALT、AST、TBIL水平无变化;与模型组相比,甲氨蝶呤组大鼠血清中ALT、AST水平显著升高(P<0.01),伸筋草高剂量组大鼠血清中ALT、AST、TBIL水平无变化。结论伸筋草治疗RA的疗效与临床常用药甲氨蝶呤相当,未表现出肝毒性,与甲氨蝶呤相比更安全。

Objective To compare the efficacy and safety(hepatotoxicity) of Lycopodii Herba and methotrexate in treatment of rheumatoid arthritis. Methods Forty SD male rats were randomly divided into control group, model group, methotrexate group, Lycopodii Herba high-dose and low-dose group. RA model was induced by bovine collagen-incomplete Freund’s adjuvant. The therapeutic efficacy of Lycopodii Herba and methotrexate in treatment of RA were systematically compared by detecting the hind paw volume of rats and the levels of serum RF, TNF-α and IL-1β in each group. To evaluate whether there was a difference in hepatotoxicity between the two drugs, the levels of serum ALT, AST and TBIL of rats in each group were detected, that to compare the safety. Results Compared with the control group, the hind paw volume of the rats in the model group, as well as the levels of serum RF, TNF-α and IL-1β increased significantly(P < 0.01). Compared with the model group, the hind paw volume and the levels of serum RF, TNF-α and IL-1β of the rats in the high-dose and low-dose Lycopodii Herba groups, and methotrexate treatment groups obviously decreased(P < 0.05). Compared with the control group, the levels of serum ALT, AST and TBIL of the rats in the model group did not change. Compared with the model group, the levels of serum ALT and AST of the rats in the methotrexate group were significantly increased(P < 0.01);the levels of serum ALT, AST, and TBIL of the rats in the high doses of Lycopodii Herba were unchanged. Conclusion The therapeutic efficacy of Lycopodii Herba is similar to methotrexate which commonly used in clinical treatment of RA. However, there was no obvious toxicity to the liver and it showed greater safety than methotrexate.