栀子油对小鼠急性酒精性肝损伤的保护作用
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摘要
研究栀子油对酒精所致小鼠急性肝损伤的保护作用。将72只小鼠随机分为正常组,模型组,栀子油低、中、高剂量组(0.3、0.6、1.2 g/kg)和阳性对照组(联苯双酯滴丸,200 mg/kg),每组12只,正常组和模型组灌胃等量的0.5%吐温-80溶液。采用改良后的造模方法(连续给药10 d后灌胃56%乙醇,15 m L/kg,连续灌胃2次)建立小鼠急性肝损伤模型,测定小鼠血清中AST、ALT、γ-GT和TG水平,检测肝组织匀浆中ADH、SOD、MDA、GSH和GSH-Px的含量,RT-PCR检测肝组织中TNF-αmRNA的表达量,HE染色光学显微镜分析小鼠肝损伤程度。结果表明:与模型组相比,栀子油各剂量组均能降低血清ALT、AST、γ-GT和TG的含量,提高ADH、GSH、GSH-Px、SOD活性,降低肝组织MDA的产生,下调TNF-αmRNA的相对表达量,肝组织变性及坏死等病理症状明显改善,尤以栀子油高剂量组效果最佳。栀子油对酒精所致小鼠急性肝损伤有保护作用,其保护机制可能与增强肝组织脂质代谢水平、提高抗氧化酶体系活力、抑制氧化应激反应及炎性因子表达相关。
The protective effect of Gardenia oil against alcohol-induced acute hepatic injury in mice was investigated. Totally 72 mice were randomly divided into normal group,model group,low,medium and high dose group( 0. 3,0. 6,1. 2 g/kg) and positive control group( bifendate pill,200 mg/kg),12 mice in each group,and the normal group and the model group were treated with an equal amount of 0. 5%Tween-80 solution. The acute liver injury model was induced by modified method,and the model,positive control and experimental groups were orally administrated 56% alcohol( 15 m L/kg) twice at 12 h interval on the tenth day after drugs administration. After 12 h,the mice were sacrificed to contribute blood and liver for biochemical and histological examinations. The results showed that compared with the model group,serum ALT,AST,γ-GT and TG contents reduced,ADH,GSH,GSH-Px and SOD activities improved, MDA generation and the relative expression of TNF-α mRNA decreased, and liver tissue degeneration and necrosis and other pathological symptoms improved significantly in each Gardenia oil dose group especially in the high dose group. The Gardenia oil had the protective effect against alcohol-induced acute hepatic injury which might be depended on the enhancement of lipid metabolism level of liver tissue,improvement of the antioxidant enzyme system activity,inhibition of oxidative stress and reduction of inflammation factors expression.
The protective effect of Gardenia oil against alcohol-induced acute hepatic injury in mice was investigated. Totally 72 mice were randomly divided into normal group,model group,low,medium and high dose group( 0. 3,0. 6,1. 2 g/kg) and positive control group( bifendate pill,200 mg/kg),12 mice in each group,and the normal group and the model group were treated with an equal amount of 0. 5%Tween-80 solution. The acute liver injury model was induced by modified method,and the model,positive control and experimental groups were orally administrated 56% alcohol( 15 m L/kg) twice at 12 h interval on the tenth day after drugs administration. After 12 h,the mice were sacrificed to contribute blood and liver for biochemical and histological examinations. The results showed that compared with the model group,serum ALT,AST,γ-GT and TG contents reduced,ADH,GSH,GSH-Px and SOD activities improved, MDA generation and the relative expression of TNF-α mRNA decreased, and liver tissue degeneration and necrosis and other pathological symptoms improved significantly in each Gardenia oil dose group especially in the high dose group. The Gardenia oil had the protective effect against alcohol-induced acute hepatic injury which might be depended on the enhancement of lipid metabolism level of liver tissue,improvement of the antioxidant enzyme system activity,inhibition of oxidative stress and reduction of inflammation factors expression.
引文
[1]邱萍,李相,孔德松,等.酒精性肝病发病机制研究的新进展[J].中国药理学通报,2014,30(2):160-163.
[2]赵洁,雷金艳.酒精性肝病的研究进展[J].北京中医药,2009,28(11):907-908.
[3]国家药典委员会.中华人民共和国药典:一部[M].北京:中国医药科技出版社,2015:248.
[4]孟祥乐,李红伟,李颜,等.栀子化学成分及其药理作用研究进展[J].中国新药杂志,2011,20(11):959-967.
[5]唐娜娜,张静.药用栀子化学成分研究[J].中国药师,2014,17(3):381-383.
[6]吴伟青,陈静,刘超群,等.绿茶多酚对小鼠酒精性肝损伤的保护作用[J].食品科学,2011,32(13):310-313.
[7]钟卫卫,林世德.内质网应激与肝损伤研究进展[J].世界华人消化杂志,2010,18(10):1021-1025.
[8]刘亮亮,刘万顺,韩宝芹,等.壳寡糖、氨基葡萄糖对酒精性肝损伤小鼠的保护作用[J].中国海洋大学学报(自然科学版),2010,40(7):73-76.
[9]邢佳,陆文娟,赵云霞,等.石榴叶多酚对小鼠急性酒精性肝损伤的保护作用[J].食品科学,2015,36(21):253-257.
[10]李静,张朝辉,段筱杉,等.大叶藻黄酮对酒精性肝损伤的保护作用[J].水产学报,2016,40(5):799-806.
[11]宋宇.生物体内乙醇脱氢酶(ADH)的活力测定、分布及其与乙醇代谢动力学的关系[D].成都:四川大学,2007.
[12]FLORA G J,SETH P K.Beneficial effects of S-adenosyl-L-methionine on aminolevulinic acid dehydratase,glutathione,and lipid peroxidation during acute leadethanol administration in mice[J].Alcohol,1999,18(2/3):103-108.
[13]MISHRA A,PAUL S,SWARNAKAR S.Down regulation of matrix metalloproteinase-9 by melatonin during prevention of alcohol-induced liver injury in mice[J].Biochimie,2011,93(5):854-866.
[14]赵云霞,陶明煊,陆文娟,等.鸡枞菌多糖对小鼠急性酒精性肝损伤的保护作用[J].食品科学,2014,35(19):260-265.
[15]DAI T,WU Y,LENG A S,et al.RXRα-regulated liver SAMe and GSH levels influence susceptibility to alcoholinduced hepatotoxicity[J].Exp Mol Pathol,2003,75(3):194-200.
[16]ZIMMERMAN S B,TRACH S O.Estimation of macromolecule concentrations and excluded volume effects for the cytoplasm of Escherichia coli[J].J Mol Biol,1991,222(3):599-620.
[17]BAEUERLE P A.The inducible transcription factor NF-κB:regulation by distinct protein subunit[J].Biochim Biophys Acta,1991,1072(1):63-80.
[2]赵洁,雷金艳.酒精性肝病的研究进展[J].北京中医药,2009,28(11):907-908.
[3]国家药典委员会.中华人民共和国药典:一部[M].北京:中国医药科技出版社,2015:248.
[4]孟祥乐,李红伟,李颜,等.栀子化学成分及其药理作用研究进展[J].中国新药杂志,2011,20(11):959-967.
[5]唐娜娜,张静.药用栀子化学成分研究[J].中国药师,2014,17(3):381-383.
[6]吴伟青,陈静,刘超群,等.绿茶多酚对小鼠酒精性肝损伤的保护作用[J].食品科学,2011,32(13):310-313.
[7]钟卫卫,林世德.内质网应激与肝损伤研究进展[J].世界华人消化杂志,2010,18(10):1021-1025.
[8]刘亮亮,刘万顺,韩宝芹,等.壳寡糖、氨基葡萄糖对酒精性肝损伤小鼠的保护作用[J].中国海洋大学学报(自然科学版),2010,40(7):73-76.
[9]邢佳,陆文娟,赵云霞,等.石榴叶多酚对小鼠急性酒精性肝损伤的保护作用[J].食品科学,2015,36(21):253-257.
[10]李静,张朝辉,段筱杉,等.大叶藻黄酮对酒精性肝损伤的保护作用[J].水产学报,2016,40(5):799-806.
[11]宋宇.生物体内乙醇脱氢酶(ADH)的活力测定、分布及其与乙醇代谢动力学的关系[D].成都:四川大学,2007.
[12]FLORA G J,SETH P K.Beneficial effects of S-adenosyl-L-methionine on aminolevulinic acid dehydratase,glutathione,and lipid peroxidation during acute leadethanol administration in mice[J].Alcohol,1999,18(2/3):103-108.
[13]MISHRA A,PAUL S,SWARNAKAR S.Down regulation of matrix metalloproteinase-9 by melatonin during prevention of alcohol-induced liver injury in mice[J].Biochimie,2011,93(5):854-866.
[14]赵云霞,陶明煊,陆文娟,等.鸡枞菌多糖对小鼠急性酒精性肝损伤的保护作用[J].食品科学,2014,35(19):260-265.
[15]DAI T,WU Y,LENG A S,et al.RXRα-regulated liver SAMe and GSH levels influence susceptibility to alcoholinduced hepatotoxicity[J].Exp Mol Pathol,2003,75(3):194-200.
[16]ZIMMERMAN S B,TRACH S O.Estimation of macromolecule concentrations and excluded volume effects for the cytoplasm of Escherichia coli[J].J Mol Biol,1991,222(3):599-620.
[17]BAEUERLE P A.The inducible transcription factor NF-κB:regulation by distinct protein subunit[J].Biochim Biophys Acta,1991,1072(1):63-80.