短肽(Pro-His-Pro,PHP)预防酒精性肝损伤

Effect of tripeptide Pro-His-Pro on alleviating alcoholic liver injury

采用脯氨酸-组氨酸-脯氨酸(Pro-His-Pro,PHP)分别处理人源肝细胞LO2和酒精性肝损伤小鼠,研究PHP是否能够缓解由肝细胞氧化损伤和食用酒精对小鼠造成的肝损伤。构建肝细胞氧化应激模型,通过不同浓度PHP处理后,检测抗氧化酶相关含量,评价氧化相关蛋白情况。构建小鼠酒精性肝损伤模型,观察肝组织病理形态学改变及生理生化和氧化相关指标。与偶氮二异丁脒盐酸盐(2,2′-azobis-2-methyl-propanimidamide,AAPH)处理组相比较,不同浓度的PHP处理组会导致抗氧化酶升高;在氧化通路方面,细胞核内核转录因子E2相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)蛋白增加,胞质Kelch ECH相关蛋白1(Kelch like ECH associated protein 1,Keap1)蛋白增多。与食用酒精组相比较,PHP处理组小鼠肝组织细胞变性程度较轻,相关指标均恢复正常,抗氧化酶氧化升高。短肽PHP可以通过调控氧化相关指标和氧化通路关键蛋白Nrf2来达到预防酒精性肝损伤的目的。

Tripeptide Pro-His-Pro(PHP)was used to treat LO2 cells and alcoholic liver injury mice respectively.It was verified in vivo and in vitro to study whether PHP can alleviate the liver injury caused by 2,2′-azobis-2-methyl-propanimidamide(AAPH)to hepatocytes and edible alcohol to mice,and to provide relevant ideas for alleviating liver injury.Oxidative stress model was constructed with LO2 cells.The cells were divided into normal group and PHP treatment group.The contents of superoxide dismutase(SOD),catalase(CAT),glutathione reduction(GSH)and malondialdehyde(MDA)in cell lysate were detected.The oxidation related marker proteins were evaluated by Western Blot.Alcoholic liver model was established with C57 BL/6 J mice.The pathomorphological changes of liver were observed,the physiological and biochemical indexes and oxidation related indexes in liver were detected.The results showed that compared with the alcohol group,the liver tissue of PHP treatment group showed less mild degeneration of hepatocytes,the levels of ALT and AST in serum decreased,the levels of TC,TG and LDL-C decreased,and the levels of HDL-C increased.The increase of CAT,GSH and SOD levels,the decrease of MDA(P<0.05).Peptide PHP can alleviate liver injury by regulating oxidation related indexes and key protein Nrf2 of oxidation pathway.