姜黄素类似物L6H4对非酒精性脂肪性肝病大鼠肝细胞Sirt1及凋亡相关蛋白表达的影响
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摘要
目的探讨姜黄素类似物L6H4对非酒精性脂肪性肝病大鼠肝细胞沉默信息调节因子1(Sirt1)及凋亡相关蛋白表达的影响。方法 36只SD大鼠随机均分为三组:对照组(C组)、高脂饮食组(F组)和姜黄素组(L组)。C组给予基础饲料,F组和L组给予高脂饲料喂养,从第9周开始L组用姜黄素类似物L6H4 0.2mg/kg灌胃,C组和F组给予相同体积的1%羧甲基纤维素钠灌胃。于第20周末处死,HE染色和Masson染色观察肝组织的病理形态变化,测定丙二醛(MDA)含量、超氧化物歧化酶(SOD)活力以及Sirt1、Bcl-2、Bax和Caspase-3 mRNA及蛋白的表达。结果 C组大鼠肝小叶结构完整,肝细胞呈单层放射状排列;F组大鼠肝小叶结构消失,细胞严重脂肪样变,部分肝细胞坏死伴有炎症细胞浸润;L组大鼠肝小叶结构部分消失,脂肪样变及肝细胞的坏死程度较F组减轻。与C组相比,F组肝组织SOD活力及Sirt1、Bcl-2 mRNA和蛋白表达降低(P<0.05),MDA含量及Bax、Caspase-3mRNA和蛋白表达升高(P<0.05);与F组相比,L组肝组织SOD活力及Sirt1、Bcl-2mRNA和蛋白表达升高(P<0.05),MDA含量及Bax、Caspase-3mRNA和蛋白表达降低(P<0.05)。结论姜黄素类似物L6H4对非酒精性脂肪性肝病大鼠肝脏具有保护作用;其机制可能是通过调控调节蛋白Bcl-2、Bax和Caspase-3的表达以及上调肝细胞Sirt1的表达来减轻氧化应激而发挥作用。
Objective To investigate the effects of curcumin analogue L6H4 on the the expressions of silent information regulator 1(Sirt1)and apoptosis proteins in rat liver of non-alcoholic fatty liver disease.Methods Tirty-six SD rats were equally divided into three groups.Group C was given normal diet and groups of F and L were given high fat diet.On the 9~(th) week,group L was gavaged with curcumin analogue L6H4 0.2 mg/kg,rats in groups of C and F were gavaged with the same volume of 1% carboxyl methyl cellulose.At the end of 20~(th) week,the pathological changes of liver were observed by HE staining and Masson staining.The levels of malonaldehyde(MDA)and superoxide dismutase(SOD)and the expressions of Sirt1,Bcl-2,Bax and Caspase-3 were detected.Results The structure of hepatic lobule in group C was integrated and hepatocytes were arranged in single radial.The structure of hepatic lobule in group F was disappeared and serious steatosis and necrosis were seen in hepatocytes.The structure of hepatic lobule in group L was disappeared partly and steatosis and necrosis of hepatocytes were alleviated compared to group F.Compared to group C,the vitality of SOD and the mRNA and protein expressions of Sirt1 and Bcl-2 were lower and level of MDA and those of Bax and Caspase-3 were higher in group F(P<0.05).Compared to group F,the vitality of SOD and the mRNA and protein expressions of Sirt1 and Bcl-2 were higher and level of MDA and those of Bax and Caspase-3 were lower in group L(P<0.05).Conclusion Curcumin analogue L6H4 can protect the liver of rat with non-alcoholic fatty liver disease.The possible mechanism is related to regulating the protein expressions of Bcl-2,Bax and Caspase-3 and upregulating Sirt1 expression,which benefits to attenuate oxidative stress.
Objective To investigate the effects of curcumin analogue L6H4 on the the expressions of silent information regulator 1(Sirt1)and apoptosis proteins in rat liver of non-alcoholic fatty liver disease.Methods Tirty-six SD rats were equally divided into three groups.Group C was given normal diet and groups of F and L were given high fat diet.On the 9~(th) week,group L was gavaged with curcumin analogue L6H4 0.2 mg/kg,rats in groups of C and F were gavaged with the same volume of 1% carboxyl methyl cellulose.At the end of 20~(th) week,the pathological changes of liver were observed by HE staining and Masson staining.The levels of malonaldehyde(MDA)and superoxide dismutase(SOD)and the expressions of Sirt1,Bcl-2,Bax and Caspase-3 were detected.Results The structure of hepatic lobule in group C was integrated and hepatocytes were arranged in single radial.The structure of hepatic lobule in group F was disappeared and serious steatosis and necrosis were seen in hepatocytes.The structure of hepatic lobule in group L was disappeared partly and steatosis and necrosis of hepatocytes were alleviated compared to group F.Compared to group C,the vitality of SOD and the mRNA and protein expressions of Sirt1 and Bcl-2 were lower and level of MDA and those of Bax and Caspase-3 were higher in group F(P<0.05).Compared to group F,the vitality of SOD and the mRNA and protein expressions of Sirt1 and Bcl-2 were higher and level of MDA and those of Bax and Caspase-3 were lower in group L(P<0.05).Conclusion Curcumin analogue L6H4 can protect the liver of rat with non-alcoholic fatty liver disease.The possible mechanism is related to regulating the protein expressions of Bcl-2,Bax and Caspase-3 and upregulating Sirt1 expression,which benefits to attenuate oxidative stress.
引文
[1]Chalasani N,Younossi Z,Lavine JE,et al.The diagnosis and management of non-alcoholic fatty liver disease:practice guideline by the American Association for the Study of Liver Diseases,American College of Gastroenterology,and the American Gastroenterological Association[J].Am J Gastroenterol,2012,107(6):811-826.
[2]Dajani A,AbuHammour A.Treatment of nonalcoholic fatty liver disease:where do we stand?An overview[J].Saudi J Gastroenterol,2016,22(2):91-105.
[3]Singal AK,Jampana SC,Weinman SA.Antioxidants as therapeutic agents for liver disease[J].Liver Int,2011,31(10):1432-1448.
[4]Inzaugarat ME,De Matteo E,Baz P,et al.New evidence for the therapeutic potential of curcumin to treat nonalcoholic fatty liver disease in humans[J].PLoS One,2017,12(3):e0172900.
[5]黄婷婷,赵丽娟,姜双燕,等.姜黄素对非酒精性脂肪性肝病大鼠环氧合酶2表达的影响[J].江苏医药,2018,44(3):243-245.
[6]Ahmed M.Non-alcoholic fatty liver disease in 2015[J].World J Hepatol,2015,7(11):1450-1459.
[7]Rolo AP,Teodoro JS,Palmeira CM.Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis[J].Free Radic Biol Med,2011,52(1):59-69.
[8]Wang L,Lv Y,Yao H,et al.Curcumin prevents the non-alcoholic fatty hepatitis via mitochondria protection and apoptosis reduction[J].Int J Clin Exp Pathol,2015,8(9):11503-11509.
[9]Colak Y,Ozturk O,Senates E,et al.SIRT1as a potential therapeutic target for treatment of nonalcoholic fatty liver disease[J].Med Sci Monit,2011,17(5):HY5-HY9.
[10]Ding RB,Bao J,Deng CX.Emerging roles of SIRT1in fatty liver diseases[J].Int J Biol Sci,2017,13(7):852-867.
[11]CantóC,Houtkooper RH,Pirinen E,et al.The NAD(+)precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity[J].Cell Metab,2012,15(6):838-847.
[2]Dajani A,AbuHammour A.Treatment of nonalcoholic fatty liver disease:where do we stand?An overview[J].Saudi J Gastroenterol,2016,22(2):91-105.
[3]Singal AK,Jampana SC,Weinman SA.Antioxidants as therapeutic agents for liver disease[J].Liver Int,2011,31(10):1432-1448.
[4]Inzaugarat ME,De Matteo E,Baz P,et al.New evidence for the therapeutic potential of curcumin to treat nonalcoholic fatty liver disease in humans[J].PLoS One,2017,12(3):e0172900.
[5]黄婷婷,赵丽娟,姜双燕,等.姜黄素对非酒精性脂肪性肝病大鼠环氧合酶2表达的影响[J].江苏医药,2018,44(3):243-245.
[6]Ahmed M.Non-alcoholic fatty liver disease in 2015[J].World J Hepatol,2015,7(11):1450-1459.
[7]Rolo AP,Teodoro JS,Palmeira CM.Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis[J].Free Radic Biol Med,2011,52(1):59-69.
[8]Wang L,Lv Y,Yao H,et al.Curcumin prevents the non-alcoholic fatty hepatitis via mitochondria protection and apoptosis reduction[J].Int J Clin Exp Pathol,2015,8(9):11503-11509.
[9]Colak Y,Ozturk O,Senates E,et al.SIRT1as a potential therapeutic target for treatment of nonalcoholic fatty liver disease[J].Med Sci Monit,2011,17(5):HY5-HY9.
[10]Ding RB,Bao J,Deng CX.Emerging roles of SIRT1in fatty liver diseases[J].Int J Biol Sci,2017,13(7):852-867.
[11]CantóC,Houtkooper RH,Pirinen E,et al.The NAD(+)precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity[J].Cell Metab,2012,15(6):838-847.