中强度耐力运动与大蒜素对高脂饮食致脂肪肝模型大鼠具有协同抵抗效应
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摘要
背景:近年来,高脂饮食及运动缺乏导致非酒精性脂肪肝发病率逐年上升。耐力运动和大蒜素均可改善血脂代谢,但有关耐力运动联合大蒜素抗高脂饮食大鼠脂肪肝形成作用方面的研究非常少见。目的:探讨中强度耐力运动联合大蒜素抗高脂饮食大鼠脂肪肝形成作用。方法:实验方案经广西师范大学动物实验伦理委员会批准。选择成年雄性SD大鼠60只,随机分为普通饮食对照组、高脂饮食组、高脂饮食安慰剂组、高脂饮食运动组、高脂饮食大蒜素组及高脂饮食运动联合大蒜素组。普通饮食对照组大鼠采用普通饲料喂养,其余组大鼠采用高脂饲料喂养,均自由饮食;高脂饮食大蒜素组、高脂饮食运动联合大蒜素组大鼠给予大蒜素液灌胃;高脂饮食安慰剂组则用同等体积剂量的蒸馏水灌胃。此外,高脂饮食运动组、高脂饮食运动联合大蒜素组大鼠进行耐力跑锻炼,每天30 min、每天1次、每周6 d。观察大鼠肝脏血红素加氧酶1蛋白表达及其活性、丙二醛含量等的变化,观察血液谷丙转氨酶、谷草转氨酶及三酰甘油、游离脂肪酸、总胆固醇等浓度变化;观察肝组织形态学变化并计算非酒精性脂肪肝活动度积分。结果与结论:(1)高脂饮食引起大鼠血液三酰甘油、游离脂肪酸、总胆固醇及谷丙转氨酶、谷草转氨酶等浓度显著升高(P <0.05),导致肝脏血红素加氧酶1活性显著下降及丙二醛含量显著升高(P <0.05),且肝脏出现明显脂肪变性、非酒精性脂肪肝活动度积分显著升高(P <0.05);(2)与高脂饮食组相比,高脂饮食运动组、高脂饮食运动联合大蒜素组脂肝脏血红素加氧酶1蛋白表达及血红素加氧酶1活性显著升高(P <0.05);(3)与高脂饮食组相比,高脂饮食运动组、高脂饮食大蒜素组、高脂饮食运动联合大蒜素组血液三酰甘油、游离脂肪酸、总胆固醇及谷丙转氨酶、谷草转氨酶等浓度显著下降(P <0.05),肝脏丙二醛含量显著下降(P <0.05),肝组织脂肪变性得到明显改善且非酒精性脂肪肝活动度积分显著下降(P <0.05);上述变化以高脂饮食运动联合大蒜素组最明显;(4)结果说明,中强度耐力运动与大蒜素对高脂饮食大鼠脂肪肝形成具协同抵抗效应,可能与二者对肝脏脂质过氧化反应及血液三酰甘油、游离脂肪酸、总胆固醇浓度升高等方面的协同控制作用有关。
BACKGROUND: The incidence of non-alcoholic fatty liver induced by high-fat diet and sports deficiency is on a rise. Endurance exercise and allicin can improve blood lipid metabolism, but the protective effect of endurance exercise combined with allicin from fatty liver formation in rats induced by high-fat diet is rarely reported.OBJECTIVE: To investigate the effect of moderate-intensity endurance exercise combined with allicin on the formation of fatty liver in rats fed with high-fat diet.METHODS: The study was approved by the Experimental Animal Ethics Committee of Guangxi Normal University. Sixty adult male Sprague-Dawley rats were randomly divided into normal diet control group, high-fat diet group, high-fat diet placebo(distilled water via gavage)group, high-fat diet exercise group, high-fat diet allicin group and high-fat diet exercise combined with allicin(allicin via gavage) group. The endurance exercise was performed for 30 minutes once daily, 6 days/week. The expression and activity of heme oxygenase-1 protein and malondialdehyde content in rat liver were detected. The concentration changes of alanine aminotransferase, glutamic oxalate aminotransferase, triglyceride, free fatty acid and total cholesterol in blood were measured. The morphological changes of liver tissue were observed and the activity integral of non-alcoholic fatty liver was calculated.RESUITS AND CONCLUSION:(1) High-fat diet significantly increased blood triglyceride, free fatty acid, total cholesterol, alanine aminotransferase and glutamic oxalate aminotransferase(P < 0.05), decreased liver heme oxygenase-1 activity and increased malondialdehyde content(P < 0.05), and increased liver steatosis and non-alcoholic fatty liver activity integral(P < 0.05).(2) Compared with the high-fat diet group, the expression level and activity of heme oxygenase-1 protein in the lipid liver of the high-fat diet exercise, high-fat diet exercise, high-fat diet exercise, high-fat diet allicin, and high-fat diet exercise combined with allicin groups were significantly increased(P <0.05).(3) Compared with the high-fat diet group, in the high-fat diet exercise, high-fat diet combined with allicin group, the blood triglycerides,free fatty acid, total cholesterol, concentration of alanine aminotransferase and glutamic oxalate aminotransferase were decreased significantly(P < 0.05); the content of malondialdehyde in liver was decreased significantly(P < 0.05); the fatty degeneration of liver tissue was improved significantly; and the activity score of non-alcoholic fatty liver decreased significantly(P < 0.05). The above changes were most obvious in the high-fat diet and exercise combined with allicin group.(4) In summary, moderate-intensity endurance exercise and allicin have synergistic resistance to fatty liver formation in rats fed with high-fat diet, which may be related to the synergistic control of lipid peroxidation in liver, triglyceride, free fatty acid and total cholesterol concentration in blood.
BACKGROUND: The incidence of non-alcoholic fatty liver induced by high-fat diet and sports deficiency is on a rise. Endurance exercise and allicin can improve blood lipid metabolism, but the protective effect of endurance exercise combined with allicin from fatty liver formation in rats induced by high-fat diet is rarely reported.OBJECTIVE: To investigate the effect of moderate-intensity endurance exercise combined with allicin on the formation of fatty liver in rats fed with high-fat diet.METHODS: The study was approved by the Experimental Animal Ethics Committee of Guangxi Normal University. Sixty adult male Sprague-Dawley rats were randomly divided into normal diet control group, high-fat diet group, high-fat diet placebo(distilled water via gavage)group, high-fat diet exercise group, high-fat diet allicin group and high-fat diet exercise combined with allicin(allicin via gavage) group. The endurance exercise was performed for 30 minutes once daily, 6 days/week. The expression and activity of heme oxygenase-1 protein and malondialdehyde content in rat liver were detected. The concentration changes of alanine aminotransferase, glutamic oxalate aminotransferase, triglyceride, free fatty acid and total cholesterol in blood were measured. The morphological changes of liver tissue were observed and the activity integral of non-alcoholic fatty liver was calculated.RESUITS AND CONCLUSION:(1) High-fat diet significantly increased blood triglyceride, free fatty acid, total cholesterol, alanine aminotransferase and glutamic oxalate aminotransferase(P < 0.05), decreased liver heme oxygenase-1 activity and increased malondialdehyde content(P < 0.05), and increased liver steatosis and non-alcoholic fatty liver activity integral(P < 0.05).(2) Compared with the high-fat diet group, the expression level and activity of heme oxygenase-1 protein in the lipid liver of the high-fat diet exercise, high-fat diet exercise, high-fat diet exercise, high-fat diet allicin, and high-fat diet exercise combined with allicin groups were significantly increased(P <0.05).(3) Compared with the high-fat diet group, in the high-fat diet exercise, high-fat diet combined with allicin group, the blood triglycerides,free fatty acid, total cholesterol, concentration of alanine aminotransferase and glutamic oxalate aminotransferase were decreased significantly(P < 0.05); the content of malondialdehyde in liver was decreased significantly(P < 0.05); the fatty degeneration of liver tissue was improved significantly; and the activity score of non-alcoholic fatty liver decreased significantly(P < 0.05). The above changes were most obvious in the high-fat diet and exercise combined with allicin group.(4) In summary, moderate-intensity endurance exercise and allicin have synergistic resistance to fatty liver formation in rats fed with high-fat diet, which may be related to the synergistic control of lipid peroxidation in liver, triglyceride, free fatty acid and total cholesterol concentration in blood.
引文
[1]娜日苏,包纳日斯.非酒精性脂肪肝的发病机制与流行病学的研究进展[J].中国医药指南,2016,14(3):39-40.
[2]Shen F,Zheng R,Shi J,et al.Impact of skin capsular distance on the performance of controlled attenuation parameter in patients with chronic liver disease.Liver Int.2015;35(11):2392-2400.
[3]范建高.非酒精性脂肪性肝病的研究现状与展望[J].临床肝胆病杂志,2015,31(7):999-1001.
[4]El-Kashef DH,El-Kenawi AE,Suddek GM,et al.Protective effect of allicin against gentamicin-induced nephrotoxicity in rats.Int Immunopharmacol.2015;29(2):679-686.
[5]许思毛,王蕊,刑荣鑫,等.大蒜素预处理对大负荷运动后大鼠心肌保护作用及其机制探讨[J].体育科学,2018,38(11):66-74.
[6]Pérez-K?hler B,García-Moreno F,Bayon Y,et al.Inhibition of staphylococcus aureus adhesion to the surface of a reticular heavyweight polypropylenemesh soaked in a combination of chlorhexidine and al icin:an in vitro study.PloS One.2015;10(5):e0126711.
[7]周媛媛,刘春杰,楚宪襄,等.大蒜素对非酒精性脂肪性肝病模型大鼠的治疗作用及TNF-α蛋白,SREBP-1c蛋白的影响[J].中国实验方剂学杂志,2016,22(13):127-130.
[8]Gao XY,Geng XJ,Zhai WL,et al.Effect of combined treatment with cyclophosphamidum and allicin on neurobloma-bearing mice.Asian Pac J Trop Med.2015;8(2):137-141.
[9]Elkayam A,Peleg E,Grossman E,et al.Effects of allicin on cardiovascular risk factors in spontaneously hypertensive rats.Isr Med Assoc J.2013;15(3):170-173.
[10]Beadford TG,Tipton CM,Wilson NC,et al.Maximum oxygen consumption of rats and its changes with various experimental procedures.J Appl Physiol.1979;47(6):1278-1283.
[11]American College of Sports Medicine.ACSM's guidelines for exercise testing and prescription.9th ed.Philadelphia(PA):Lippincott Williams&Wilkins.2013.
[12]Kleiner DE,Brunt EM,Van Natta M,et al.Design and validation of a histological scoring system for nonalcoholic fatty liver disease.Hepatology.2005;41(6):1313-1321.
[13]李海玲,彭书明,李凛,等.4种常用蛋白浓度测定方法的比较[J].中国生化药物杂志,2008,29(4):277-278,282.
[14]杨家耀,时昭红,马威,等.附子理中汤通过激活AMPK通路及抑制NF-κBp65通路降低非酒精性脂肪肝大鼠肝脏损伤[J].中国中药杂志,2018,43(15):3176-3183.
[15]徐正婕,范建高,王国良,等.高脂饮食致大鼠非酒精性脂肪性肝炎肝纤维化模型[J].世界华人消化杂志,2002,10(4):392-396.
[16]张建民,张娜娜,崔璀,等.薏苡仁提取物改善大鼠非酒精性脂肪肝游离脂肪酸的代谢机制研究[J].中国药师,2017,20(1):25-29.
[17]穆杰,王庆国,王雪茜,等.非酒精性脂肪肝机制及其与慢性应激相关性的研究进展[J].世界华人消化杂志,2016,24(5):692-698.
[18]李青艳,王绩凯,冯哲伟,等.非酒精性脂肪肝患者脂质过氧化与肝功能的相关性研究[J].重庆医学,2012,41(16):1591-1592.
[19]张艳,卢洁,周莹群,等.非酒精性脂肪性肝病与氧化应激[J].世界临床药物,2013,34(8):459-463.
[20]李颖.“二次打击”假说与非酒精性脂肪肝[J].医学综述,2013,19(4):594-596.
[21]Vergnes L,Chin RG,DE Aguiar Vallim T,et al.SREBP-2-deficient and hypomorphic mice reveal roles for SREBP-2 in embryonic development and SREBP-1c expression.J Lipid Res.2016;57(3):410-421.
[22]Lai SJ,Li Y,Kuang Y,et al.PKC delta silencing alleviates saturated fatty acid induced ER stress by enhancing SERCA activity.Biosci Rep.2017;37(6):1-10.
[23]杜杰.有氧运动结合燕麦β-葡聚糖对高脂仓鼠降低胆固醇的作用及机制[J].中国体育科技,2017,53(1):97-103.
[24]苗华,张旭,赵英永.基于代谢组学研究有氧运动对高脂血症的治疗作用及其生物化学作用机制[J]北京体育大学学报,2015,38(12):78-82,101.
[25]Guo R,Liong EC,So KF,et al.Beneficial mechanisms of aerobic exercise on hepatic lipid metabolism in non-alcoholic fatty liver disease.Hepatobiliary Pancreat Dis Int.2015;14(2):139-444
[26]Sertie RA,Andreotti,Proena AR,et al.Cessation of physical exercise changes metabolism and modifies the adipocyte cellularity of the periepididymal white adipose tissue in rats.J Appl Physiol(1985).2013;115(3):394-402.
[27]Elkayam A,Peleg E,Grossman E,et al.Effects of allicin on cardiovascular risk factors in spontaneously hypertensive rats.Isr Med Assoc J.2013;15(3):170-173.
[28]杨莉.大蒜改善血脂代谢紊乱研究进展[J].中成药,2016,38(3):634-638.
[29]李国峰,许思毛.运动经PKC-Nfr2途径调节肝血红素加氧酶-1表达及抗氧化能力的研究[J].广西师范大学学报(自然科学版),2017,35(1):113-118.
[2]Shen F,Zheng R,Shi J,et al.Impact of skin capsular distance on the performance of controlled attenuation parameter in patients with chronic liver disease.Liver Int.2015;35(11):2392-2400.
[3]范建高.非酒精性脂肪性肝病的研究现状与展望[J].临床肝胆病杂志,2015,31(7):999-1001.
[4]El-Kashef DH,El-Kenawi AE,Suddek GM,et al.Protective effect of allicin against gentamicin-induced nephrotoxicity in rats.Int Immunopharmacol.2015;29(2):679-686.
[5]许思毛,王蕊,刑荣鑫,等.大蒜素预处理对大负荷运动后大鼠心肌保护作用及其机制探讨[J].体育科学,2018,38(11):66-74.
[6]Pérez-K?hler B,García-Moreno F,Bayon Y,et al.Inhibition of staphylococcus aureus adhesion to the surface of a reticular heavyweight polypropylenemesh soaked in a combination of chlorhexidine and al icin:an in vitro study.PloS One.2015;10(5):e0126711.
[7]周媛媛,刘春杰,楚宪襄,等.大蒜素对非酒精性脂肪性肝病模型大鼠的治疗作用及TNF-α蛋白,SREBP-1c蛋白的影响[J].中国实验方剂学杂志,2016,22(13):127-130.
[8]Gao XY,Geng XJ,Zhai WL,et al.Effect of combined treatment with cyclophosphamidum and allicin on neurobloma-bearing mice.Asian Pac J Trop Med.2015;8(2):137-141.
[9]Elkayam A,Peleg E,Grossman E,et al.Effects of allicin on cardiovascular risk factors in spontaneously hypertensive rats.Isr Med Assoc J.2013;15(3):170-173.
[10]Beadford TG,Tipton CM,Wilson NC,et al.Maximum oxygen consumption of rats and its changes with various experimental procedures.J Appl Physiol.1979;47(6):1278-1283.
[11]American College of Sports Medicine.ACSM's guidelines for exercise testing and prescription.9th ed.Philadelphia(PA):Lippincott Williams&Wilkins.2013.
[12]Kleiner DE,Brunt EM,Van Natta M,et al.Design and validation of a histological scoring system for nonalcoholic fatty liver disease.Hepatology.2005;41(6):1313-1321.
[13]李海玲,彭书明,李凛,等.4种常用蛋白浓度测定方法的比较[J].中国生化药物杂志,2008,29(4):277-278,282.
[14]杨家耀,时昭红,马威,等.附子理中汤通过激活AMPK通路及抑制NF-κBp65通路降低非酒精性脂肪肝大鼠肝脏损伤[J].中国中药杂志,2018,43(15):3176-3183.
[15]徐正婕,范建高,王国良,等.高脂饮食致大鼠非酒精性脂肪性肝炎肝纤维化模型[J].世界华人消化杂志,2002,10(4):392-396.
[16]张建民,张娜娜,崔璀,等.薏苡仁提取物改善大鼠非酒精性脂肪肝游离脂肪酸的代谢机制研究[J].中国药师,2017,20(1):25-29.
[17]穆杰,王庆国,王雪茜,等.非酒精性脂肪肝机制及其与慢性应激相关性的研究进展[J].世界华人消化杂志,2016,24(5):692-698.
[18]李青艳,王绩凯,冯哲伟,等.非酒精性脂肪肝患者脂质过氧化与肝功能的相关性研究[J].重庆医学,2012,41(16):1591-1592.
[19]张艳,卢洁,周莹群,等.非酒精性脂肪性肝病与氧化应激[J].世界临床药物,2013,34(8):459-463.
[20]李颖.“二次打击”假说与非酒精性脂肪肝[J].医学综述,2013,19(4):594-596.
[21]Vergnes L,Chin RG,DE Aguiar Vallim T,et al.SREBP-2-deficient and hypomorphic mice reveal roles for SREBP-2 in embryonic development and SREBP-1c expression.J Lipid Res.2016;57(3):410-421.
[22]Lai SJ,Li Y,Kuang Y,et al.PKC delta silencing alleviates saturated fatty acid induced ER stress by enhancing SERCA activity.Biosci Rep.2017;37(6):1-10.
[23]杜杰.有氧运动结合燕麦β-葡聚糖对高脂仓鼠降低胆固醇的作用及机制[J].中国体育科技,2017,53(1):97-103.
[24]苗华,张旭,赵英永.基于代谢组学研究有氧运动对高脂血症的治疗作用及其生物化学作用机制[J]北京体育大学学报,2015,38(12):78-82,101.
[25]Guo R,Liong EC,So KF,et al.Beneficial mechanisms of aerobic exercise on hepatic lipid metabolism in non-alcoholic fatty liver disease.Hepatobiliary Pancreat Dis Int.2015;14(2):139-444
[26]Sertie RA,Andreotti,Proena AR,et al.Cessation of physical exercise changes metabolism and modifies the adipocyte cellularity of the periepididymal white adipose tissue in rats.J Appl Physiol(1985).2013;115(3):394-402.
[27]Elkayam A,Peleg E,Grossman E,et al.Effects of allicin on cardiovascular risk factors in spontaneously hypertensive rats.Isr Med Assoc J.2013;15(3):170-173.
[28]杨莉.大蒜改善血脂代谢紊乱研究进展[J].中成药,2016,38(3):634-638.
[29]李国峰,许思毛.运动经PKC-Nfr2途径调节肝血红素加氧酶-1表达及抗氧化能力的研究[J].广西师范大学学报(自然科学版),2017,35(1):113-118.