大花红景天提取物对DMF致小鼠肝损伤的保护作用及其机制研究

The study on protective effect and its mechanism of Rhodiola crenulata extract on liver injury induced by N,N-dimethylformamide in mice

目的探讨大花红景天水提物(aqueous extract of Rhodiola crenulata,RCE)对二甲基甲酰胺(N,N-dimethylformamide,DMF)致小鼠肝损伤的保护作用及其机制。方法 ICR小鼠按体重随机分为6组:对照组、RCE组(400 mg/kg RCE)、DMF组(1500 mg/kg DMF)、低剂量联合处理组(100 mg/kg RCE+1500 mg/kg DMF)、中剂量联合处理组(200 mg/kg RCE+1500 mg/kg DMF)和高剂量联合处理组(400 mg/kg RCE+1500 mg/kg DMF)。对照组和DMF组每天灌胃双蒸水,RCE组以400 mg/kg RCE灌胃,联合处理组分别先以100、200及400 mg/kg的RCE灌胃,1次/d,共5 d。DMF组及联合处理组于最后一次灌胃30 min后腹腔注射1500 mg/kg DMF生理盐水溶液,对照组及RCE组注射同体积生理盐水。48 h后处死动物,测定血清ALT、AST、LDH活性和总胆汁酸(TBA)含量,肝MDA、SOD、还原型谷胱甘肽(GSH)、氧化型谷胱甘肽(GSSG)和8-羟基脱氧鸟苷(8-OHdG)水平。结果与对照组比较,DMF组血清ALT、AST、LDH活性、血清TBA及肝MDA含量明显升高(P<0.05),肝SOD活力降低(P<0.05),肝8-OHdG含量升高。与DMF组比较,各剂量联合处理组血清ALT和AST活性、TBA含量均降低(P<0.05),中、高剂量联合处理组血清LDH活性和肝MDA含量降低(P<0.05),低剂量联合处理组肝SOD活力升高(P<0.05),各剂量联合处理组肝8-OHdG含量降低。结论大花红景天水提物对DMF所致小鼠肝损伤有保护作用,可能与大花红景天的抗氧化作用有关。

Objective To investigate the protective effect and its mechanism of aqueous extract from the root of Rhodiola crenulata（RCE） on liver injury induced by N,N-dimethylformamide（DMF） in mice.Methods ICR mice were randomly divided into 6 groups： control group,RCE group（400 mg/kg RCE）,DMF group（1500 mg/kg DMF）,low,medium and high doses of RCE ＋ DMF combined treatment groups（100 mg/kg RCE＋1500 mg/kg DMF,200 mg/kg RCE＋1500 mg/kg DMF,and 400 mg/kg RCE＋1500 mg/kg DMF,respectively）.While double distilled water was intragastrically given to mice in control group and DMF group,mice in combined treatment groups and RCE group received different doses of RCE（100,200,400 and 400 mg/kg,respectively）for 5 days.DMF（1500 mg/kg） was（ip） given into the mice in DMF group and three combined treatment groups 30 min after intragastrical administrations on the fifth day,while same volume of 0.9%NaCl was（ip） given into mice in control group and RCE group.All of the mice were euthanized 48h after administration of DMF or 0.9%NaCl.The activities of serum alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,and lactate dehydrogenase（LDH）,contents of total bile acid（TBA） were determined.The contents of GSH,GSSG,MDA and 8-hydroxy-2′-deoxyguanosine（8-OHdG）,activities of SOD in liver were measured.Results Compared with control group,the activities of serum ALT,AST and LDH,serum TBA levels and liver MDA of mice in DMF group were significantly increased,the activities of liver SOD were decreased（P0.05）,the contents of 8-OHdG in liver were increased.Compared with DMF group,the activities of serum ALT and AST,levels of serum TBA of mice in three combined treatment groups were significantly decreased,the activities of serum LDH and liver MDA contents of mice in medium and high doses of RCE ＋ DMF combined treatment groups were significantly decreased,liver SOD activities of mice in low dose of RCE ＋ DMF combined treatment group were increased（P0.05）,and the contents of 8-OHdG in liver of mice in three combined treatment groups were partly decreased.Conclusion RCE could have an obviously protective effect against DMF-induced hepatotoxicity in mice,which could be associated with the antioxidative effect of Rhodiola crenulata.