乳源免疫调节肽对小鼠急性酒精性肝损伤的保护作用
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摘要
目的研究乳源免疫调节肽对小鼠急性酒精性肝损伤的保护作用。方法将60只清洁级♂昆明种小鼠随机分为正常组、模型组、乳源免疫调节肽(PGPIPN)低、中、高剂量组和阳性对照谷胱甘肽(GSH)组。连续灌胃2周,最后3 d,采用白酒(56度)给小鼠连续灌胃建立急性酒精性肝损伤模型,测定各组小鼠体质量、肝脏指数及相关生化指标;取肝脏制作组织切片HE染色,观察肝组织的病理学变化。结果模型组小鼠血清中谷丙转氨酶(alanine aminotransferase,ALT)和谷草转氨酶(aspartate aminotransferase,AST)明显高于正常对照组,肝组织出现了肝索排列紊乱,肝细胞坏死,炎性细胞浸润。与模型组相比,PGPIPN高剂量组肝脏指数、血清ALT、AST水平较模型组明显降低。PGPIPN高剂量组TNF-α含量较模型组明显减少,肝组织中谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、超氧化物歧化酶(superoxidedismutase,SOD)活性增强,丙二醛(malondialdehyde,MDA)水平明显下降;肝组织病理损伤也得到明显改善。结论 PGPIPN对小鼠急性酒精性肝损伤具有较好的保护作用。
Aim To investigate the protective effect of immunomodulating peptide( PGPIPN) on the acute alcoholic liver injury in mice. Methods Kunming mice were randomly divided into control group, model group,glutataione( GSH) group, PGPIPN low dose group,PGPIPN moderate and high dose groups. The mice were treated with different doses of PGPIPN or GSH for two weeks except control group and model group. The acute alcoholic liver injury model was induced by gavage with 56° alcohol for three days. The indices including the activities of AST,ALT in serum,and the contents of TNF-α,MDA,SOD and GSH-Px in liver were examined. Liver histopathological changes were examined by HE staining. Results Compared with control group,the levels of serum ALT,AST and the contents of TNF-α,MDA significantly increased,while the contents of SOD and GSH-Px significantly decreased in model group. There was hepatocyte apoptosis and inflammatory cell infiltration in liver tissues.Compared with model group,the activities of serum ALT,AST and the contents of TNF-α,MDA were remarkably reduced in PGPIPN high dose group. The contents of SOD and GSH-Px significantly increased in PGPIPN high dose group. PGPIPN could alleviate the injury of liver. Conclusion PGPIPN has certain protective effect on acute alcoholic liver injury of mice,providing a theoretical guidance.
Aim To investigate the protective effect of immunomodulating peptide( PGPIPN) on the acute alcoholic liver injury in mice. Methods Kunming mice were randomly divided into control group, model group,glutataione( GSH) group, PGPIPN low dose group,PGPIPN moderate and high dose groups. The mice were treated with different doses of PGPIPN or GSH for two weeks except control group and model group. The acute alcoholic liver injury model was induced by gavage with 56° alcohol for three days. The indices including the activities of AST,ALT in serum,and the contents of TNF-α,MDA,SOD and GSH-Px in liver were examined. Liver histopathological changes were examined by HE staining. Results Compared with control group,the levels of serum ALT,AST and the contents of TNF-α,MDA significantly increased,while the contents of SOD and GSH-Px significantly decreased in model group. There was hepatocyte apoptosis and inflammatory cell infiltration in liver tissues.Compared with model group,the activities of serum ALT,AST and the contents of TNF-α,MDA were remarkably reduced in PGPIPN high dose group. The contents of SOD and GSH-Px significantly increased in PGPIPN high dose group. PGPIPN could alleviate the injury of liver. Conclusion PGPIPN has certain protective effect on acute alcoholic liver injury of mice,providing a theoretical guidance.
引文
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[12]夏婷,张瑾,姚佳慧,等.氧化应激在酒精性肝病中作用机制的研究进展[J].中国药理学通报,2017,33(10):1353-6.[12]Xia T,Zhang J,Yao J H,et al.Research progress in mechanism of oxidative stress in alcoholic liver disease[J].Chin Pharmacol Bull,2017,33(10):1353-6.
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[15]Masalkar P D.Oxidative stress and antioxidant status in patients with alcoholic liver disease[J].Clin Chim Acta,2005,355(1-2):61-5.
[2]Wang H,Ma L,Yin Q,et al.Prevalence of alcoholic liver disease and its association with socioeconomic status in north-eastern China[J].Alcohol Clin Exp Res,2014,38(4):1035-41.
[3]刘国涛,朱玉翠,张涛,等.酒精性肝病研究进展[J].世界华人消化杂志,2017,25(15):1382-8.[3]Liu G T,Zhu Y C,Zhang T,et al.Advances in research of alcoholic liver disease[J].World Chin J Digestol,2017,25(15):1382-8.
[4]赵丽.肝水解肽治疗肝炎肝硬化疗效观察[J].中国当代医药,2011,18(26):62-3.[4]Zhao L.Efficacy observation of liver hydrolysates in treatment of liver cirrhosis[J].China Mod Med,2011,18(26):62-3.
[5]刘睿,任金威,陈启贺,等.人参低聚肽对急性酒精性肝损伤大鼠的保护作用[J].现代预防医学,2016,43(15):2820-4.[5]Liu R,Ren J W,Chen Q H,et al.Protective effects of panax ginseng oligopeptide on acute alcohol-induced liver injury and underlying mechanism[J].Mod Prev Med,2016,43(15):2820-4.
[6]秦宜德,邹思湘.乳中生物活性物质的研究进展[J].食品科学,2004,25(3):188-92.[6]Qin Y D,Zou S X.Research progress on biological active substances in milk[J].Food Sci,2004,25(3):188-92.
[7]Politis I.Milk peptides and immune response in the neonate[J].Alcohol Clin Exp Res,2008,606:253-69.
[8]顾芳,秦宜德,董华胜,等.乳源免疫调节肽对小鼠抗氧化和抗疲劳作用研究[J].营养学报,2006,28(4):326-8.[8]Gu F,Qin Y D,Dong H S,et al.Effects of immunomodulating peptide fromβ-casein on antioxidation and anti-fatigue in mice[J].Acta Nutrim Sin,2006,28(4):326-8.
[9]董华胜,秦宜德,李素萍,等.乳源免疫调节肽具有促进体内外淋巴细胞转化的作用[J].中国药理学通报,2007,23(1):73-6.[9]Dong H S,Qin Y D,Li S P,et al.Effects of immunomodulating peptide fromβ-casein on lymphocyte transformation both in vivo and in vitro[J].Chin Pharmacol Bull,2007,23(1):73-6.
[10]Wang W,Gu F,Wei C,et al.PGPIPN,a therapeutic hexapeptide,suppressed human ovarian cancer growth by targeting Bcl-2[J].PLo S One,2013,8(4):e60701.
[11]石小枫,刘杞,郭树华.还原型谷胱甘肽对小鼠急性肝损伤的保护作用[J].现代医药卫生,2002,18(10):849-50.[11]Shi X F,Liu Q,Guo S H.Effect of glutathione on acute liver injury in mice[J].Mod Med Health,2002,18(10):849-50.
[12]夏婷,张瑾,姚佳慧,等.氧化应激在酒精性肝病中作用机制的研究进展[J].中国药理学通报,2017,33(10):1353-6.[12]Xia T,Zhang J,Yao J H,et al.Research progress in mechanism of oxidative stress in alcoholic liver disease[J].Chin Pharmacol Bull,2017,33(10):1353-6.
[13]Zhou J Y,Jiang Z A,Zhao C Y,et al.Long-term binge and escalating ethanol exposure causes necroinflammation and fibrosis in rat liver[J].Alcohol Clin Exp Res,2013,37(2):213-22.
[14]高潇雪,刘立新.酒精性肝病流行病学及发病机制研究进展[J].中华消化病与影像杂志(电子版),2016,6(4):62-5.[14]Gao X X,Liu L X.Progress in the epidemiology and pathogenesis of alcoholic liver diseases[J].Chin J Digest Med Imageol(Electron Ed),2016,6(4):62-5.
[15]Masalkar P D.Oxidative stress and antioxidant status in patients with alcoholic liver disease[J].Clin Chim Acta,2005,355(1-2):61-5.