人参枳椇子提取物对小鼠酒精性肝损伤的保护作用
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摘要
目的:研究人参枳椇子提取物对酒精所致小鼠急性肝损伤的保护作用。方法:不同配伍比例的人参枳椇子提取物以100 mg/kg的剂量连续灌胃小鼠3 d后,除正常组外,其余各组小鼠给予体积分数为50%的乙醇(6 g/kg·bw)灌胃,建立一次性暴饮小鼠急性酒精性肝损伤模型。在给予酒精12 h后处死小鼠,检测各组小鼠血清中天冬氨酸氨基转移酶(Aspartate aminotransferase,AST)、丙氨酸氨基转移酶(Alanine aminotransferase,ALT)的活力及甘油三酯(Triglyceride,TG)、高密度脂蛋白胆固醇(High-density lipoproteins,HDL-C)、低密度脂蛋白胆固醇(Low-density lipoproteins,LDL-C)的含量,肝脏中谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-Px)、超氧化物歧化酶(Superoxide dismutase,SOD)的活力及还原型谷胱甘肽(Glutathione,GSH)、丙二醛(Malondialdehyde,MDA)含量。利用酶联免疫吸附法测定血清中肿瘤坏死因子α(TNF-α)、白介素-1β(IL-1β)的含量变化,并用反转录PCR法检测TNF-α和IL-1β的基因表达水平。结果:与模型组小鼠比较,人参枳椇子提取物能够明显降低由急性酒精摄入引起的血清中AST、ALT活力的升高(p <0.05);降低血清中TG、LDL-C的含量(p <0.05),升高HDL-C的水平(p <0.05),改善脂质代谢失衡;提高肝组织中抗氧化酶SOD和GSH-Px的活力(p <0.05),减少肝组织中GSH损耗并抑制肝组织中MDA含量增加(p <0.05),提高抗氧化能力保护肝脏损伤;下调炎症因子TNF-α、IL-1β的表达来减轻炎症损伤(p <0.05)。结论:人参枳椇子提取物对急性酒精诱导的小鼠肝损伤有明显的保护作用。
The potential protective effects of water extract from Panax ginseng and Hovenia dulcis Thunb( PHE) on mice with alcohol-induced liver injury were evaluated in this paper. METHODS: PHE,which obtained by different compatibility ratio of Panax ginseng and Hovenia dulcis Thunb,were gavaged to mice with at a dose of 100 mg/kg for 3 d. Acute liver injury was established by gavage of 50% ethanol. After oral administration of content of alcohol for 12 h,the levels of aspartate aminotransferase( AST),alanine aminotransferase( ALT),triglyceride( TG),high-density lipoproteins( HDL-C) and low-density( LDL-C) in serum,as well as the activities of glutathione peroxidase( GSH-Px),superoxide dismutase( SOD),glutathione( GSH) and malondialdehyde( MDA) in liver were measured. The levels of TNF-α and IL-1β in the serum were measured by enzyme-linked immunosorbent assay( ELISA) and the mRNA expressions of TNF-α and IL-1β in liver tissure were detected by reverse transcription polymerase chain reaction( RT-PCR). RESULTS: As Compared with the model group,PHE could significantly reduce the activities of AST and ALT in serum.PHE could significantly inhibit the imbalance of lipid metabolism by reducing the content of serum TG and LDL-C( p < 0.05) and increasing the level of HDL-C( p < 0.05).Meanwhile,PHE could also improve antioxidant capability against liver injury by enhancing the activities of SOD and GSH-Px( p < 0.05),increasing the level of GSH and decreasing the content of MDA in liver tissue( p < 0.05). PHE adjusted the inflammatory response through decreasing the level of TNF-α and IL-1β( p < 0.05). Conclusion: PHE indicated obvious protective effect on mice with acute alcohol-induced liver injury in mice.
The potential protective effects of water extract from Panax ginseng and Hovenia dulcis Thunb( PHE) on mice with alcohol-induced liver injury were evaluated in this paper. METHODS: PHE,which obtained by different compatibility ratio of Panax ginseng and Hovenia dulcis Thunb,were gavaged to mice with at a dose of 100 mg/kg for 3 d. Acute liver injury was established by gavage of 50% ethanol. After oral administration of content of alcohol for 12 h,the levels of aspartate aminotransferase( AST),alanine aminotransferase( ALT),triglyceride( TG),high-density lipoproteins( HDL-C) and low-density( LDL-C) in serum,as well as the activities of glutathione peroxidase( GSH-Px),superoxide dismutase( SOD),glutathione( GSH) and malondialdehyde( MDA) in liver were measured. The levels of TNF-α and IL-1β in the serum were measured by enzyme-linked immunosorbent assay( ELISA) and the mRNA expressions of TNF-α and IL-1β in liver tissure were detected by reverse transcription polymerase chain reaction( RT-PCR). RESULTS: As Compared with the model group,PHE could significantly reduce the activities of AST and ALT in serum.PHE could significantly inhibit the imbalance of lipid metabolism by reducing the content of serum TG and LDL-C( p < 0.05) and increasing the level of HDL-C( p < 0.05).Meanwhile,PHE could also improve antioxidant capability against liver injury by enhancing the activities of SOD and GSH-Px( p < 0.05),increasing the level of GSH and decreasing the content of MDA in liver tissue( p < 0.05). PHE adjusted the inflammatory response through decreasing the level of TNF-α and IL-1β( p < 0.05). Conclusion: PHE indicated obvious protective effect on mice with acute alcohol-induced liver injury in mice.
引文
[1]Orman E S,Odena G,Bataller R.Alcoholic liver disease:Pathogenesis,management,and novel targets for therapy[J].Journal of Gastroenterology and Hepatology,2013,28(1):77-84.
[2]孙晓梅,阎姝,田书霞.中药治疗肝损伤的研究进展[J].中药材,2016,39(11):2661-2664.
[3]石燕燕,李树才,孙军.人参皂苷Rg3通过PI3K/AKT信号系统调控Ca M基因表达促进胃癌BGC-823细胞的凋亡[J].中国肿瘤生物治疗杂志,2018,25(6):590-594.
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[6]Li F,Wu X,Li J,et al.Ginsenoside Rg1ameliorates hippocampal long-term potentiation and memory in an Alzheimer’s disease model[J].Molecular Medicine Reports,2016,13(6):4904-4910.
[7]彭沛,宋志明,刘勇,等.人参皂苷Rb1抗小鼠脑自然衰老及其对m TOR/p70S6K通路的影响[J].中山大学学报,2015,36(2):176-180.
[8]李渊,周玥,王亚平,等.人参皂苷Rg1基于SIRT6/NF-κB信号通路对辐射致造血干/祖细胞衰老的保护作用[J].中草药,2017,48(27):4497-4501.
[9]Yao X,Jiang W,Ma C H,et al.Protective effects of ginsenoside Rg1against carbon tetrachloride-induced liver injury in mice through suppression of inflammation[J].Phytomedicine,2016,23(6):583-588.
[10]Li J P,Gao Y,Chu S F,et al.Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1in a rat model of acohol-and CCl4-induced hepatic fibrosis[J].Acta Pharmacologica Sinica,2014,35(8):1031-1044.
[11]Kim H G,Jang S S,Lee J S,et al.Panax ginseng Meyer prevents radiation-induced liver injury via modulation of oxidative stress and apoptosis[J].Journal of Ginseng Research,2017,41(2):159-168.
[12]嵇杨,杨平,李俊.枳椇子对乙醇所致小鼠肝脏损伤的预防作用[J].中药药理与临床,2000,16(3):19-20.
[13]陈春晓,朱肖鸿.酒精性肝炎大鼠模型建立及枳椇子的干预作用[J].浙江中西医结合杂志,2007,17(5):285-287.
[14]梁赅,詹莉,汪晖,等.人参和枳椇子对小鼠乙醇急性中毒保护作用及其机制研究[J].医学新知杂志,2006,16(2):82-83.
[15]齐慧慧,宋佳,陈岳祥.小鼠急性酒精性肝损伤模型的建立[J].世界华人消化杂志,2012,20(9):759-763.
[16]Khattab H,Fouad A,Hamza M,et al.Relation of ALT and AST levels to the histopathological changes in liver biopsies of patients with chronic hepatitis C genotype 4[J].Arab Journal of Gastroenterology,2015,16(2):50-53.
[17]Tang L Y,Chen Y,Rui B B,et al.Resveratrol ameliorates lipid accumulation in Hep G2 cells,associated with downregulation of lipin1 expression[J].Canadian Journal of Physiology and Pharmacology,2016,94(2):185-189.
[18]张巧红,徐艳玲,杨靖华,等.人参皂苷干预酒精性脂肪肝形成的实验研究及对小鼠抗氧化应激的影响[J].中华中医药学刊,2016,34(12):2970-2973.
[19]Ding R B,Tian K,Cao Y W,et al.Protective effect of Panax notoginseng saponins on acute ethanol-induced liver injury is associated with ameliorating hepatic lipid accumulation and reducing ethanol-mediated oxidative stress[J].Journal of Agricultural and Food Chemistry,2015,63(9):2413-2422.
[20]Wu D,Cederbaum A I.Alcohol,oxidative stress,and free radical damage[J].Alcohol Research&Health,2003,27(4):277-284.
[21]Koch O R,Pani G,Borrello S,et al.Oxidative stress and antioxidant defenses in ethanol-induced cell injury[J].Molecular Aspects of Medicine,2004,25(1-2):191-198.
[22]黄川锋,王海鑫,康爱英,等.辛夷对急性酒精性肝损伤小鼠的肝保护作用及机制研究[J].中国临床药理学杂志,2015,31(7):515-518.
[23]Li G,Ye Y,Kang J,et al.l-Theanine prevents alcoholic liver injury through enhancing the antioxidant capability of hepatocytes[J].Food and Chemical Toxicology,2012,50(2):363-372.
[24]Park H Y,Choi H D,Eom H,et al.Enzymatic modification enhances the protective activity of citrus flavonoids against alcohol-induced liver disease[J].Food Chemistry,2013,139(1-4):231-240.
[25]Szabo G,Mandrekar P.A recent perspective on alcohol,immunity,and host defense[J].Alcoholism,Clinical and Experimental research,2009,33(2):220-232.
[26]Gao B,Bataller R.Alcoholic liver disease:Pathogenesis and new therapeutic targets[J].Gastroenterology,2011,141(5):1572-1585.
[27]杨万枝,吕雄文.酒精性肝病发病机制研究进展[J].安徽医科大学学报,2012,47(1):97-99.
[28]Wu D,Cederbaum A I.Oxidative stress and alcoholic liver disease[J].Seminars in Liver Disease,2009,29(2):141-154.
[29]Assun92o M,Santos-Marques M J,Monteiro R,et al.Red wine protects against ethanol-induced oxidative stress in rat liver[J].Journal of Agricultural and Food Chemistry,2009,57(14):6066-6073.
[30]Albano E.Free radical mechanisms in immune reactions associated with alcoholic liver disease[J].Free Radical Biology and Medicine,2002,32(2):110-114.
[2]孙晓梅,阎姝,田书霞.中药治疗肝损伤的研究进展[J].中药材,2016,39(11):2661-2664.
[3]石燕燕,李树才,孙军.人参皂苷Rg3通过PI3K/AKT信号系统调控Ca M基因表达促进胃癌BGC-823细胞的凋亡[J].中国肿瘤生物治疗杂志,2018,25(6):590-594.
[4]Li B H,Zhao J O,Wang C Z,et al.Ginsenoside Rh2induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53[J].Cancer Letters,2011,301(2):185-192.
[5]崔秀明,徐珞珊,王强.人参皂苷Rb3的抗血小板和抗血栓作用[J].中成药,2006,28(10):1526-1528.
[6]Li F,Wu X,Li J,et al.Ginsenoside Rg1ameliorates hippocampal long-term potentiation and memory in an Alzheimer’s disease model[J].Molecular Medicine Reports,2016,13(6):4904-4910.
[7]彭沛,宋志明,刘勇,等.人参皂苷Rb1抗小鼠脑自然衰老及其对m TOR/p70S6K通路的影响[J].中山大学学报,2015,36(2):176-180.
[8]李渊,周玥,王亚平,等.人参皂苷Rg1基于SIRT6/NF-κB信号通路对辐射致造血干/祖细胞衰老的保护作用[J].中草药,2017,48(27):4497-4501.
[9]Yao X,Jiang W,Ma C H,et al.Protective effects of ginsenoside Rg1against carbon tetrachloride-induced liver injury in mice through suppression of inflammation[J].Phytomedicine,2016,23(6):583-588.
[10]Li J P,Gao Y,Chu S F,et al.Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1in a rat model of acohol-and CCl4-induced hepatic fibrosis[J].Acta Pharmacologica Sinica,2014,35(8):1031-1044.
[11]Kim H G,Jang S S,Lee J S,et al.Panax ginseng Meyer prevents radiation-induced liver injury via modulation of oxidative stress and apoptosis[J].Journal of Ginseng Research,2017,41(2):159-168.
[12]嵇杨,杨平,李俊.枳椇子对乙醇所致小鼠肝脏损伤的预防作用[J].中药药理与临床,2000,16(3):19-20.
[13]陈春晓,朱肖鸿.酒精性肝炎大鼠模型建立及枳椇子的干预作用[J].浙江中西医结合杂志,2007,17(5):285-287.
[14]梁赅,詹莉,汪晖,等.人参和枳椇子对小鼠乙醇急性中毒保护作用及其机制研究[J].医学新知杂志,2006,16(2):82-83.
[15]齐慧慧,宋佳,陈岳祥.小鼠急性酒精性肝损伤模型的建立[J].世界华人消化杂志,2012,20(9):759-763.
[16]Khattab H,Fouad A,Hamza M,et al.Relation of ALT and AST levels to the histopathological changes in liver biopsies of patients with chronic hepatitis C genotype 4[J].Arab Journal of Gastroenterology,2015,16(2):50-53.
[17]Tang L Y,Chen Y,Rui B B,et al.Resveratrol ameliorates lipid accumulation in Hep G2 cells,associated with downregulation of lipin1 expression[J].Canadian Journal of Physiology and Pharmacology,2016,94(2):185-189.
[18]张巧红,徐艳玲,杨靖华,等.人参皂苷干预酒精性脂肪肝形成的实验研究及对小鼠抗氧化应激的影响[J].中华中医药学刊,2016,34(12):2970-2973.
[19]Ding R B,Tian K,Cao Y W,et al.Protective effect of Panax notoginseng saponins on acute ethanol-induced liver injury is associated with ameliorating hepatic lipid accumulation and reducing ethanol-mediated oxidative stress[J].Journal of Agricultural and Food Chemistry,2015,63(9):2413-2422.
[20]Wu D,Cederbaum A I.Alcohol,oxidative stress,and free radical damage[J].Alcohol Research&Health,2003,27(4):277-284.
[21]Koch O R,Pani G,Borrello S,et al.Oxidative stress and antioxidant defenses in ethanol-induced cell injury[J].Molecular Aspects of Medicine,2004,25(1-2):191-198.
[22]黄川锋,王海鑫,康爱英,等.辛夷对急性酒精性肝损伤小鼠的肝保护作用及机制研究[J].中国临床药理学杂志,2015,31(7):515-518.
[23]Li G,Ye Y,Kang J,et al.l-Theanine prevents alcoholic liver injury through enhancing the antioxidant capability of hepatocytes[J].Food and Chemical Toxicology,2012,50(2):363-372.
[24]Park H Y,Choi H D,Eom H,et al.Enzymatic modification enhances the protective activity of citrus flavonoids against alcohol-induced liver disease[J].Food Chemistry,2013,139(1-4):231-240.
[25]Szabo G,Mandrekar P.A recent perspective on alcohol,immunity,and host defense[J].Alcoholism,Clinical and Experimental research,2009,33(2):220-232.
[26]Gao B,Bataller R.Alcoholic liver disease:Pathogenesis and new therapeutic targets[J].Gastroenterology,2011,141(5):1572-1585.
[27]杨万枝,吕雄文.酒精性肝病发病机制研究进展[J].安徽医科大学学报,2012,47(1):97-99.
[28]Wu D,Cederbaum A I.Oxidative stress and alcoholic liver disease[J].Seminars in Liver Disease,2009,29(2):141-154.
[29]Assun92o M,Santos-Marques M J,Monteiro R,et al.Red wine protects against ethanol-induced oxidative stress in rat liver[J].Journal of Agricultural and Food Chemistry,2009,57(14):6066-6073.
[30]Albano E.Free radical mechanisms in immune reactions associated with alcoholic liver disease[J].Free Radical Biology and Medicine,2002,32(2):110-114.