自然发酵驼乳对乙醇诱导的小鼠急性肝损伤的保护作用
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摘要
研究自然发酵驼乳对小鼠急性酒精性肝损伤的保护作用。将24只雄性ICR小鼠随机分为正常组、模型组和自然发酵驼乳组。连续灌胃两周后,给小鼠灌胃50%乙醇溶液(7.3 g/kg)建立肝损伤模型。测定各组小鼠体质量、肝脏指数以及血清和肝脏的相关生化指标;将肝脏组织进行HE染色,观察肝组织病理学变化。结果显示:与对照组比较,模型组血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)的活性以及促炎细胞因子的含量显著增加(p<0.05或p<0.01),肝组织病理切片显示出明显的损伤和大量炎性细胞浸润。与模型组相比,自然发酵驼乳组ALT活性显著下降(p<0.05),肿瘤坏死因子-α(TNF-α)及白细胞介素-1β(IL-1β)含量极显著降低(p<0.01)。HE染色的结果显示小鼠肝组织中炎性细胞浸润明显减少,脂肪变性程度减轻。肝脏丙二醛(MDA)含量显著下降(p<0.05),超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性显著升高(p<0.05),肝脏甘油三酯(TG)含量极显著降低(p<0.01)。结果表明,自然发酵驼乳对小鼠急性酒精性肝损伤有较好的保护作用,这可能与降低小鼠体内炎症应答水平和改善肝脏氧化应激程度有关。
To study the protective effects of naturally fermented camel milk on acute alcoholic liver injury in mice. 24 male SPF CD-1(ICR)mice were randomly divided into 3 groups,the normal control group,model control group,and naturally fermented camel milk group. After a two week administration,the acute alcohol liver injury mouse model was set up by intragastric administration of alcohol in the dose of 7.3 g/kg. Body weight,liver index,serum and liver biochemical indicators were measured in each group.The pathologicalchanges of liver were observed by light microscope with HE staining. The result showed that,compared with the control group,activities of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and proinflammatory cytokines contents of serum in the model group were significantly increased(p<0.05 or p<0.01). The liver histopathological sections also showed significant injury and extensive inflammatory cell infiltration. Compared with the model group,the ALT activities of the naturally fermented camel milk group decreased significantly(p<0.05),and the contents of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)decreased significantly(p<0.01). The results of HE staining showed that the inflammatory cell infiltration in the liver tissue was significantly reduced,and the degree of steatosis was reduced. The contents of malondialdehyde(MDA)in the liver of naturally fermented camel milk group was significantly decreased(p<0.05),the activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)was significantly increased(p<0.05),and the contents of TG was significantly lower than that of the model group(p<0.01).The results show that naturally fermented camel milk has a good protective effect on acute alcoholic liver injury in mice,which exert its beneficial effects mainly through reducing the contents of inflammatory response in body and improving the oxidative stress in the liver of mice.
To study the protective effects of naturally fermented camel milk on acute alcoholic liver injury in mice. 24 male SPF CD-1(ICR)mice were randomly divided into 3 groups,the normal control group,model control group,and naturally fermented camel milk group. After a two week administration,the acute alcohol liver injury mouse model was set up by intragastric administration of alcohol in the dose of 7.3 g/kg. Body weight,liver index,serum and liver biochemical indicators were measured in each group.The pathologicalchanges of liver were observed by light microscope with HE staining. The result showed that,compared with the control group,activities of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and proinflammatory cytokines contents of serum in the model group were significantly increased(p<0.05 or p<0.01). The liver histopathological sections also showed significant injury and extensive inflammatory cell infiltration. Compared with the model group,the ALT activities of the naturally fermented camel milk group decreased significantly(p<0.05),and the contents of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)decreased significantly(p<0.01). The results of HE staining showed that the inflammatory cell infiltration in the liver tissue was significantly reduced,and the degree of steatosis was reduced. The contents of malondialdehyde(MDA)in the liver of naturally fermented camel milk group was significantly decreased(p<0.05),the activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)was significantly increased(p<0.05),and the contents of TG was significantly lower than that of the model group(p<0.01).The results show that naturally fermented camel milk has a good protective effect on acute alcoholic liver injury in mice,which exert its beneficial effects mainly through reducing the contents of inflammatory response in body and improving the oxidative stress in the liver of mice.
引文
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[7]宋之臻.当归多糖肝靶向作用及保护急性肝损伤机理的研究[D].武汉:华中科技大学,2016.
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[9]Zhao J,Chen H,Li Y.Protective effect of bicyclol on acute alcohol-induced liver injury in mice[J].European Journal of Pharmacology,2008,586(1-3):322-331.
[10]Gao B,Bataller R.Alcoholic liver disease:Pathogenesis and new therapeutic targets[J].Gastroenterology,2011,141(5):1572-1585.
[11]Zhang H,Chen X,Dan T,et al.Traditional Chinese fermented dairy foods[M]//Lactic Acid Bacteria.Springer Netherlands,2014.
[12]Polychroniadou A.Handbook of Milk of Non-Bovine Mammals[J].2007,60(4):304-305.
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[14]Nanji A A,Khettry U,Sadrzadeh S M H.Lactobacillus feeding reduces endotoxemia and severity of experimental alcoholic liver(disease)[J].Proceedings of the Society for Experimental Biology and Medicine,1994,205(3):243-247.
[15]张哲,刘小鸣,陈卫.内蒙古传统发酵驼乳中乳酸菌和酵母菌的分离鉴定及其生物多样性分析[J].中国食品学报,2018,18(7).
[16]孙天松,刘红霞,倪慧娟,等.传统发酵酸驼乳中乳酸菌的分离及鉴定[J].中国乳品工业,2006,34(9).
[17]Guicciardi M E,Gores G J.Apoptosis:A mechanism of acute and chronic liver injury[J].Gut,2005,54(7):1024-1033.
[18]Tilg H,Moschen A R,Szabo G.Interleukin-1 and inflammasomes in alcoholic liver disease/acute alcoholic hepatitis and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis[J].Hepatology,2016,64(3):955-965.
[19]Yan A W,Fouts D E,Brandl J,et al.Enteric dysbiosis associated with a mouse model of alcoholic liver disease[J].Hepatology,2011,53(1):96-105.
[20]Chen P,Miyamoto Y,Mazagova M,et al.Microbiota protects mice against acute alcohol-induced liver injury[J].Alcoholism Clinical and Experimental Research,2015,39(12):2313-2323.
[21]Schnabl B,Brenner D A.Interactions between the intestinal microbiome and liver diseases[J].Gastroenterology,2014,146(6):1513-1524.
[22]Lucey M R,Mathurin P,Morgan T R.Alcoholic hepatitis[J].The New England Journal of Medicine,2009,360(26):2758-2769.
[23]Albano E,Vidali M.Immune mechanisms in alcoholic liver disease[J].Genes & Nutrition,2010,5(2):141-147.
[24]Beermann C,Hartung J.Physiological properties of milk ingredients released by fermentation[J].Food & Function,2013,4(2):185-199.
[25]乌仁图雅.双峰驼自然发酵乳对小鼠抗应激和抗氧化能力的影响[D].内蒙古农业大学,2010.
[26]You M,Fischer M,Deeg M A,et al.Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element-binding protein(SREBP)[J].The Journal of Biological Chemistry,2002,277(32):29342-29347.
[27]Nakajima T,Kamijo Y,Tanaka N,et al.Peroxisome proliferator-activated receptor alpha protects against alcohol-induced liver damage[J].Hepatology,2004,40(4):972-980.
[28]Yadav A K,Kumar R,Priyadarshini L,et al.Composition and medicinal properties of camel milk:A review[J].Journal of Dairying Foods & Home Sciences,2015,34(2):83.
[29]Bahobail A S,Ali A A,Alyan A A.Effect of fermentation process on the improvement of nutrition value of camel milk[J].International Journal of Multidisciplinary and Current Research,2014,2(1):78-82.
[30]Meldebekova A,Konuspayeva G,Diacono E,et al.Heavy metals and trace elements content in camel milk and shubat from Kazakhstan.In:Faye B,Sinyavskiy Y.Impact of pollution on animal products[M].Berlin:Springer Netherlands,2008:117-123.
[2]GBD 2016 alcohol collaborators.Alcohol use and burden for 195 countries and territories,1990-2016:Asystematic analysis for the global burden of disease study 2016[J].The Lancet,2018.
[3]Louvet A,Mathurin P.Alcoholic liver disease:Mechanisms of injury and targeted treatment[J].Nature Reviews Gastroenterology & Hepatology,2015,12(4):231-242.
[4]Llopis M,Cassard A M,Wrzosek L,et al.Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease[J].Gut,2016,65(5):830-839.
[5]Soleymanzadeh N,Mirdamadi S,Kianirad M.Antioxidant activity of camel and bovine milk fermented by lactic acid bacteria isolated from traditional fermented camel milk(Chal)[J].Dairy Science & Technology,2016,96(4):443-457.
[6]Forsyth C B,Farhadi A,Jakate S M,et al.Lactobacillus GG treatment ameliorates alcohol-induced intestinal oxidative stress,gut leakiness,and liver injury in a rat model of alcoholic steatohepatitis[J].Alcohol,2009,43(2):163-172.
[7]宋之臻.当归多糖肝靶向作用及保护急性肝损伤机理的研究[D].武汉:华中科技大学,2016.
[8]王志军.寡聚脱氧核苷酸对小鼠急性酒精性肝损伤的影响[D].长春:吉林大学,2012.
[9]Zhao J,Chen H,Li Y.Protective effect of bicyclol on acute alcohol-induced liver injury in mice[J].European Journal of Pharmacology,2008,586(1-3):322-331.
[10]Gao B,Bataller R.Alcoholic liver disease:Pathogenesis and new therapeutic targets[J].Gastroenterology,2011,141(5):1572-1585.
[11]Zhang H,Chen X,Dan T,et al.Traditional Chinese fermented dairy foods[M]//Lactic Acid Bacteria.Springer Netherlands,2014.
[12]Polychroniadou A.Handbook of Milk of Non-Bovine Mammals[J].2007,60(4):304-305.
[13]Adachi Y,Moore L E,Bradford B U,et al.Antibiotics prevent liver injury in rats following long-term exposure to ethanol[J].Gastroenterology,1995,108(1):218-224.
[14]Nanji A A,Khettry U,Sadrzadeh S M H.Lactobacillus feeding reduces endotoxemia and severity of experimental alcoholic liver(disease)[J].Proceedings of the Society for Experimental Biology and Medicine,1994,205(3):243-247.
[15]张哲,刘小鸣,陈卫.内蒙古传统发酵驼乳中乳酸菌和酵母菌的分离鉴定及其生物多样性分析[J].中国食品学报,2018,18(7).
[16]孙天松,刘红霞,倪慧娟,等.传统发酵酸驼乳中乳酸菌的分离及鉴定[J].中国乳品工业,2006,34(9).
[17]Guicciardi M E,Gores G J.Apoptosis:A mechanism of acute and chronic liver injury[J].Gut,2005,54(7):1024-1033.
[18]Tilg H,Moschen A R,Szabo G.Interleukin-1 and inflammasomes in alcoholic liver disease/acute alcoholic hepatitis and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis[J].Hepatology,2016,64(3):955-965.
[19]Yan A W,Fouts D E,Brandl J,et al.Enteric dysbiosis associated with a mouse model of alcoholic liver disease[J].Hepatology,2011,53(1):96-105.
[20]Chen P,Miyamoto Y,Mazagova M,et al.Microbiota protects mice against acute alcohol-induced liver injury[J].Alcoholism Clinical and Experimental Research,2015,39(12):2313-2323.
[21]Schnabl B,Brenner D A.Interactions between the intestinal microbiome and liver diseases[J].Gastroenterology,2014,146(6):1513-1524.
[22]Lucey M R,Mathurin P,Morgan T R.Alcoholic hepatitis[J].The New England Journal of Medicine,2009,360(26):2758-2769.
[23]Albano E,Vidali M.Immune mechanisms in alcoholic liver disease[J].Genes & Nutrition,2010,5(2):141-147.
[24]Beermann C,Hartung J.Physiological properties of milk ingredients released by fermentation[J].Food & Function,2013,4(2):185-199.
[25]乌仁图雅.双峰驼自然发酵乳对小鼠抗应激和抗氧化能力的影响[D].内蒙古农业大学,2010.
[26]You M,Fischer M,Deeg M A,et al.Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element-binding protein(SREBP)[J].The Journal of Biological Chemistry,2002,277(32):29342-29347.
[27]Nakajima T,Kamijo Y,Tanaka N,et al.Peroxisome proliferator-activated receptor alpha protects against alcohol-induced liver damage[J].Hepatology,2004,40(4):972-980.
[28]Yadav A K,Kumar R,Priyadarshini L,et al.Composition and medicinal properties of camel milk:A review[J].Journal of Dairying Foods & Home Sciences,2015,34(2):83.
[29]Bahobail A S,Ali A A,Alyan A A.Effect of fermentation process on the improvement of nutrition value of camel milk[J].International Journal of Multidisciplinary and Current Research,2014,2(1):78-82.
[30]Meldebekova A,Konuspayeva G,Diacono E,et al.Heavy metals and trace elements content in camel milk and shubat from Kazakhstan.In:Faye B,Sinyavskiy Y.Impact of pollution on animal products[M].Berlin:Springer Netherlands,2008:117-123.
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