苦参碱减轻对乙酰氨基酚诱导小鼠肝损伤的研究

Effects of matrine on acetaminophen-induced liver injury

目的探讨注射用盐酸苦参碱对对乙酰氨基酚(APAP)诱导的小鼠肝损伤的作用机制。方法将雄性昆明小鼠随机分为空白组、模型组和低、中、高剂量实验组,每组12只。除空白组外其余小组均腹部注射300 mg·kg^(-1)APAP进行急性肝损伤造模。低、中、高剂量实验组分别静脉注射0.7、1.4和2.8 mg·kg^(-1)苦参碱;空白组和模型组均尾部静脉注射10%葡萄糖溶液10 mL·kg^(-1)·d^(-1)。5组小鼠均治疗7 d。用酶联免疫吸附试验法检测谷草转氨酶(GOT)、谷丙转氨酶(GPT)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平,用试剂盒检测肝组织中超氧化物歧化酶(SOD)和丙二醛(MDA)的水平。结果中、高剂量实验组和模型组、空白组的血清GOT分别为(5593.45±128.46)、(2316.24±125.37)、(8302.16±267.15)和(40.13±7.69)U·L^(-1),GPT分别为(6159.37±129.64)、(2597.10±120.37)、(81699.54±259.87)和(36.47±9.46)U·L^(-1),IL-6分别为(159.43±26.42)、(96.37±25.84)、(215.34±47.68)和(83.72±26.37)pg·mL^(-1),TNF-α分别为(327.68±38.37)、(249.69±44.97)、(477.68±58.59)和(254.35±50.67)pg·mL^(-1),SOD分别为(329.46±37.49)、(371.16±33.76)、(246.84±38.79)和(429.67±23.76)U·mg^(-1),MDA分别为(5.34±0.76)、(4.09±0.54)、(12.46±3.76)和(3.12±0.42)nmol·mg^(-1)。中、高剂量实验组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P<0.05)。结论苦参碱对APAP诱导的药物性肝损伤具有显著的保护作用,其保护机制与抑制炎症反应和减轻氧化应激反应有关。

Objective To investigate the mechanism of matrine hydrochloride injection on acetaminophen(APAP)induced liver injury in mice.Methods Sixty male Kunming mice were randomly divided into blank group,model group and experimental-L,-M,-H groups.The mice were abdominal injected 300 mg·kg^(-1)APAP to build the acute liver injury modeling.The experimental-L,-M,-H groups were intravenous injected matrine of 0.7,1.4,and 2.8 mg·kg^(-1),respectively.Blank and model groups were injected with 10%glucose solution 10 mL·kg^(-1)·d^(-1) via tail vein.Enzyme-linked immunosorbent assay were used to measure the levels of glutamic oxaloacetic transaminase(GOT),glutamic oxaloacetic transaminase(GPT),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in mice serum.The kit were employed to detect the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in liver tiss ue.Results The serum GOT levels in the experimental-M,-H groups,model group and blank group were(5593.45±128.46),(2316.24±125.37),(8302.16±267.15)and(40.13±7.69)U·L^(-1);the GPT levels were(6159.37±129.64),(2597.10±120.37),(81699.54±259.87)and(36.47±9.46)U·L^(-1);the IL-6 levels were(159.43±26.42),(96.37±25.84),(215.34±47.68)and(83.72±26.37)pg·mL^(-1);the TNF-αlevels were(327.68±38.37),(249.69±44.97),(477.68±58.59)and(254.35±50.67)pg·mL^(-1);the SOD levels were(329.46±37.49),(371.16±33.76),(246.84±38.79)and(429.67±23.76)U·mg^(-1);the MDA levels were(5.34±0.76),(4.09±0.54),(12.46±3.76)and(3.12±0.42)nmol·mg^(-1).There were significant differences between the experimental-M,-H groups and the model group(all P<0.05).Conclusion Matrine has a significant protective effect on APAP induced drug-induced liver injury,and its protective mechanism is related to inhibiting inflammatory response and alleviating oxidative stress response.