不同剂量加味芍甘附子汤对胶原诱导性关节炎大鼠干预作用及安全性研究

Interventional effect and safety of modified Shaoganfuzi decoction with different doses in CIA rats

目的探讨不同剂量加味芍甘附子汤对胶原诱导性关节炎(collagen-induced arthritis,CIA)大鼠炎性细胞因子和安全性指标的影响,研究其疗效和安全性。方法Wistar大鼠36只,根据体重随机分为6组:正常组,CIA模型组,对照组及中药低、中、高剂量组,每组6只。正常组常规饲养,其余各组复制CIA寒证模型后,模型组生理盐水灌胃,对照组雷公藤多苷(6.25 mg·kg^(-1))灌胃,中药组加味芍甘附子汤低、中、高剂量(0.625、1.25、2.5 g·mL^(-1))灌胃,干预4周,测定各组大鼠关节炎症指数评分、踝关节滑膜病理学改变、外周血IL-6水平,心(肌钙蛋白)、肝(CK18、HMGB1、GLDH)、肾(NGAL、胱抑素C)早期预警及常规安全性指标。结果干预4周后,加味芍甘附子汤中、高剂量组AI评分较CIA模型组显著降低(P<0.05);病理结果显示加味芍甘附子汤各剂量组与模型组相比,关节腔狭窄、滑膜细胞增生、淋巴细胞浸润及关节面受损减轻;加味芍甘附子汤中、高剂量组血清IL-6水平较CIA模型组降低(P<0.05);各组大鼠外周血生化指标及CK18、HMGB1、胱抑素C水平组间差异无统计学意义;对照组及中药低、中、高剂量组GLDH水平较正常组降低(P<0.05);对照组NGAL水平较正常组升高(P<0.05);对照组及低剂量组肌钙蛋白水平较正常组降低(P<0.05)。结论不同剂量加味芍甘附子汤均未出现心、肝、肾脏毒性作用,并能减轻关节肿胀,降低IL-6水平,为后续相关研究和临床应用提供实验基础。

Objective To investigate the effects of different doses of modified Shaoganfuzi Decoction on inflammatory cytokines and safety indexes in rats with collagen-induced arthritis,and to study its efficacy and safety.Methods Thirtysix Wistar rats were randomly divided into 6 groups according to their body weight:normal group,CIA model group,control group,and traditional Chinese medicine group with low,medium and high dose groups,with 6 rats in each group.The normal group was fed routinely,after the CIA cold syndrome model was replicated in the other groups,the model group was gavaged with normal saline,the control group was gavaged with Tripterygium wilfordii polyglycosides(6.25mg·kg^(-1)),and the traditional Chinese medicine group was given low,medium and high doses of modified Shaoganfuzi decoction.(0.625 g·mL^(-1),1.25 g·mL^(-1),2.5 g·mL^(-1))were intragastrically administered and intervened for 4 weeks.The joint inflammation index score,the pathological changes of the ankle joint synovium and the peripheral blood inflammatory cytokine IL-6 were measured in each group.levels,and cardiac(troponin),liver(CK18,HMGB1,GLDH),kidney(NGAL,cystatin C)early warning and routine safety indicators.Results After 4 weeks of intervention,the AI scores of the middle and high dose groups of modifined Shaoganfuzi Decoction were significantly lower than those of the CIA model group(P<0.05).Stenosis,synovial cell hyperplasia,lymphocyte infiltration and articular surface damage were alleviated;serum IL-6 levels in the middle and high doses of modifined Shaoganfuzi decoction groups were lower than those in the CIA model group(P<0.05);peripheral blood biochemical changes of rats in each group There was no significant difference in the indexes and the levels of CK18,HMGB1 and cystatin C between the groups;the levels of GLDH in the control group and the low,middle and high doses of traditional Chinese medicine groups were lower than those in the normal group(P<0.05);the levels of NGAL in the control group were higher than those in the normal group(P<0.05);the levels of troponin in the control group and low-dose group were lower than those in the normal group(P<0.05).Conclusion Modified Shaoganfuzi Decoction has no toxic effects on the heart,liver and kidney,and can reduce joint swelling and IL-6 level,which provides the basis for subsequent research and clinical application.