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目的:研究雷公藤片发挥抗炎作用剂量下伴随的肝毒性作用,为其“病-效-毒”相关性研究提供理论依据。方法:80只KM小鼠,全部雄鼠,随机分为8组,每组10只,分别为正常组、模型组、雷公藤片剂量1~5组(51.48,36.55,25.74,18.28,12.87μg·kg-1)和环磷酰胺组(73 mg·kg-1),除正常组外,其余各组均以1%2,4-二硝基氟苯(DNFB)溶液建立小鼠迟发型超敏反应模型,通过给予不同剂量的雷公藤片,观察小鼠的耳肿胀度和肿胀抑制率,检测血清中前列腺素E2(PGE2),肿瘤坏死因子-α(TNF-α),白细胞介素-2(IL-2),前白蛋白(PA),丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST),总胆汁酸(TBA)和总胆红素(TBIL)等生化指标水平的变化,并计算脏器和体重的比值。结果:与正常组比较,模型组小鼠耳肿胀血清中PGE2,TNF-α,IL-2,PA含量明显升高(P<0.01);与模型组比较,雷公藤片可明显抑制迟发型超敏反应致小鼠耳肿胀血中PGE2,TNF-α和IL-2含量的降低,并呈现一定的剂量依赖性;小鼠血中ALT,AST,TBA,TBIL活性升高,PA含量降低,肝体比值变大(P<0.01)。结论:雷公藤片在14.58μg·kg-1(7.01~19.06μg·kg-1)有较强的抗炎作用,其抗炎机制与减少炎性介质的产生和释放有关。剂量14.58μg·kg-1(7.01~19.06μg·kg-1)的雷公藤片还可对小鼠肝脏产生一定的损伤。
OBJECTIVE: To study the toxic effects of Tripterygium tablets on hepatotoxicity at anti-inflammatory doses and to provide a theoretical basis for the study on its correlation to disease-drug-toxicity. Methods: Eighty KM mice and all the male rats were randomly divided into 8 groups (n = 10): normal group, model group and Tripterygium wilfordii tablet in groups 1 to 5 (51.48,36.55,25.74,18.28,12.87μg Kg-1) and cyclophosphamide (73 mg · kg-1), except the normal group, all the other groups were given 1% 2,4- dinitrofluorobenzene (DNFB) Sensitive reaction model. Tripterygium wilfordii tablet was administered at different doses to observe ear swelling and swelling inhibition rate in mice. Serum levels of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin- (IL-2), prealbumin (PA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA) and total bilirubin Biochemical indicators of the level of change, and calculate the ratio of organs and weight. Results: Compared with the normal group, the contents of PGE2, TNF-α, IL-2 and PA in the ear edema serum of the model group were significantly increased (P <0.01). Compared with the model group, Tripterygium wilfordii tablet could significantly inhibit the delayed- Sensitized mice induced ear swelling swelling PGE2, TNF-α and IL-2 levels decreased, and showed a dose-dependent; mice blood ALT, AST, TBA, TBIL activity increased, PA decreased, liver Body ratio increased (P <0.01). Conclusion: Tripterygium wilfordii tablet has a strong anti-inflammatory effect at 14.58μg · kg-1 (7.01 ~ 19.06μg · kg-1), and its anti-inflammatory mechanism is related to reducing the production and release of inflammatory mediators. Tripterygium wilfordii tablet dose 14.58μg · kg-1 (7.01 ~ 19.06μg · kg-1) can also cause some damage to the liver of mice.