余甘子提取物对小鼠急性酒精肝损伤的保护作用研究

研究余甘子提取物（extractum phyllanthus emblica,EPE）对小鼠急性酒精肝损伤的预防保护作用和机制。方法:60只雄性小鼠随机分为空白组、模型组、药物对照组（美他多辛胶囊-欣立得,200 mg/kg·d）和EPE高、中、低剂量组（400、160、80 mg/kg·d）,灌胃给药30 d,末次给药后1 h灌胃56%乙醇造急性酒精肝损伤模型。12 h后检测血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、甘油三酯（TG）、肿瘤坏死因子α（TNF-α）、白介素6（IL-6）、白介素10（IL-10）浓度,检测肝脏丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、乙醇脱氢酶（ADH）含量,实时荧光定量PCR（real time PCR）检测肝脏脂肪酸合成酶（FAS）、脂肪分化相关蛋白（ADRP）、细胞色素P450 2E1（CYP2E1）、过氧化酶体增殖激活α受体（PPARα）和半胱氨酸天冬氨酸蛋白酶3（Caspase3）mRNA的表达,HE染色观察肝脏组织病理变化。结果表明:EPE能显著降低小鼠血清ALT、AST、TG浓度,减轻肝脏病理损伤;EPE显著提高肝脏乙醇代谢酶ADH、CAT活性,下调CYP2E1 mRNA表达水平,缩短小鼠醒酒时间;EPE显著下调脂肪酸合成酶FAS和转运酶ADRP基因表达,抑制脂肪酸合成和向肝脏转运;EPE显著提高肝脏抗氧化酶SOD、GSH-Px活性,降低MDA浓度,发挥抗氧化活性保护肝脏损伤;EPE显著降低炎性因子TNF-α和IL-6浓度,减轻肝脏炎症损伤,但对IL-10浓度没有显著影响;EPE显著下调Casepase3基因表达,降低肝脏细胞凋亡水平;EPE显著上调PPARα基因表达来减轻肝脏氧化和炎症损伤。结论:EPE通过乙醇代谢酶活性调节、脂代谢调控、抗氧化损伤、抗炎和抗细胞凋亡来保护小鼠急性酒精肝损伤,具有开发为解酒护肝保健食品的前景。 

Protection and mechanism of extractum phyllanthus emblica on acute alcohol-induced liver injury in mice

To study the preventive protection effects and mechanisms of extractum phyllanthus emblica ( EPE) on acute alcoholic liver injury in mice. 60 ICR male mice were randomly divided into 6 groups, including blank group, model group, medicine contrast group ( Metadoxine Capsules, 200 mg/kg·d) , EPE group ( 80、160、400 mg/kg·d) . Medication groups were given with EPE or Metadoxine Capsules respectively by intragastric administration for 30 days.Then, acute alcoholic liver injury model was established by intragastric administration of 56% alcohol ( 13 mg/kg) to the medication and model groups 1 h later after the last administration.12 h later, the activities of serum ALT, AST, TG, TNF-α, LI-6, IL-10, the content of hepatic MDA, SOD, GSH-Px, ADH, the mRNA levels of FAS, ADRP, CYP2E1, PPARα and Caspase3 in liver were measured. HE staining was performed for observing pathological changes of the liver tissues.The results showed that EPE can significantly reduce the level of serum ALT, AST, TG and the liver pathological damage. EPE can significantly reduce the sober time by improving the activities of hepatic alcohol metabolism enzyme ADH, CAT, meanwhile EPE reduce CYP2E1 mRNA expression. EPEsignificantly suppress the synthesis and transport of fatty acid by inhibiting the expression of FAS and ADRP.EPE significantly increased the activities of SOD and GSH-Px, lower MDA concentration to protect liver injury by antioxidant activity. EPE significantly reduced the content of inflammatory factor TNF-α and IL-6 to relieve liver inflammatory lesions, but EPE had no significant effects on the IL-10 content. EPE significantly reduced the level of liver cell apoptosis by down regulating the expression of Caspase3. EPE significantly relieved liver oxidative damage and inflammatory lesions by up regulating the expression of PPARα. Conclusion: EPE by ethanol metabolic enzyme activity regulation, lipid metabolic control, resistance to oxidation damage, anti-inflammatory and anti cell apoptosis can protect acute alcoholic liver injury in mice. EPE has the prospect of development to avoid hangover and be liver protection health food.