表没食子儿茶素没食子酸酯对黄曲霉毒素B1致大鼠急性肝损伤的保护作用

摘要

Objective:To study the protective effect of epigallocatechin-3-gallate(EGCG) on acute liver injury induced by aflatoxin B1 (AFB1) in rats.Methods:Fifty SD rats were randomly divided into normal control group,model group,low-and high-dose EGCG intervention groups,and EGCG control group.The rats in the normal control and model group were administrated double distilled water via gavage for 5 days.Rats in the two intervention groups and EGCG control group were administrated 25 mg/kg,100 mg/kg and 100 mg/kg EGCG respectively via gavage for 5 days.On the 6th day,the rats in the control group and EGCG control group were injected intraperitoneally with 0.5 mL DMSO solution,and those in the model group and the two intervention groups were injected intraperitoneally with 2 mg/kg AFB1.The IL-6 level in serum and the 8-OHdG level in liver tissues were measured by enzyme-linked-immunosorbent assay(ELISA).The pathological changes of liver tissues were observed by HE staining.The mRNA expressions of IL-6,Bcl-2 and BAX were determined by qPCR.Results:Compared with the normal control group,pathological changes of hepatic tissues in the model group showed obvious punctate necrosis,hepatocyte ballooning,and inflammatory cell infiltration,whereas a significant improvement in the pathological changes of the livers could be found in the two intervention groups.The protein and mRNA levels of IL-6 as well as the 8-OHdG level in the model group were significantly increased,while the Bcl-2/BAX ratio was decreased(P＜0.05 or P ＜ 0.01).However,the IL-6 mRNA and protein levels and 8-OHdG content were reduced by EGCG administration(P ＜0.01),while the Bcl-2/BAX ratio was elevated (P ＜0.05).No significant differences were noted between the EGCG control group and the normal control group with regard to above indexes(P＞0.05).Conclusion:EGCG could protect from acute liver injury induced by AFB1 in rats,and the mechanism might be related to attenuating inflammatory response,reducing hepatocyte DNA injury and inhibiting cell apoptosis.%目的:探讨表没食子几茶素没食子酸酯(EGCG)对黄曲霉毒素B1(AFB1)致大鼠急性肝损伤的保护作用.方法:将50只SD大鼠随机分为空白对照组、模型组、低剂量EGCG干预组、高剂量EGCG干预组和EGCG对照组.空白对照组、模型组大鼠先以双蒸水连续灌胃5d,1次/d;两个干预组和EGCG对照组分别用25 mg/kg、100 mg/kg、100 mg/kg EGCG溶液连续灌胃5d,1次/d.在第6天,空白对照组和EGCG对照组大鼠予以二甲亚砜(DMSO)腹腔注射,模型组、两个干预组大鼠予以2 mg/kg剂量AFB1腹腔注射,观察2d.观察期间仍以相应溶液灌胃.第9天取所有大鼠血清测定白介素-6(IL-6)水平,取肝组织进行病理学检查,测定B细胞淋巴瘤基因-2(Bcl-2)和Bcl-2相关X蛋白(BAX)基因表达量及8-羟基脱氧鸟苷(8-OHdG)水平.结果:模型组大鼠肝组织病理切片显示明显的点状坏死、肝细胞气球样变及炎性细胞浸润,血清IL-6水平及肝组织8-OHdG水平、IL-6基因表达均高于空白对照组(P≥0.05),而Bcl-2/BAX比值低于空白对照组(P≥0.01).两个干预组大鼠肝组织病理损伤有所改善,血清IL-6水平、肝组织8-OHdG水平和IL-6基因表达均低于模型组(P≥0.01),Bcl-2/BAX比值则高于模型组(P≥0.05).EGCG对照组各项指标与空白对照组基本一致(P＞0.05).结论:EGCG对AFB1所致急性肝损伤具有保护作用,其机制可能与降低炎症程度、减少肝细胞DNA损伤和减少凋亡有关.