葱白提取物对非酒精性脂肪肝模型大鼠ACCase和CPT-1表达的影响
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摘要
目的:探讨葱白提取物治疗非酒精性脂肪肝(NAFLD)可能的作用机制。方法:60只大鼠分为正常组、模型组、低剂量葱白组、中剂量葱白组、高剂量葱白组、易善复组,每组10只。采用高脂饮食造模,造模10周后经组织病理学鉴定模型制备成功后给予不同剂量药物干预4周。光镜下观察肝组织HE染色组织结构;检测血浆黏度、全血黏度及血清三酰甘油(TG)、总胆固醇(TC)、天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)水平及肝组织游离脂肪酸(FFA)的含量;Realtime PCR检测大鼠肝脏乙酰辅酶A羧化酶(ACCase)、肉毒碱棕榈酰基转移酶-1(CPT-1)mRNA的表达情况。结果:模型组大鼠肝脏出现明显脂肪变性,舌像评分、肝指数、血浆黏度和全血黏度以及血清AST、ALT、TC、TG水平明显升高(P<0.05),ACCase mRNA表达升高(P<0.05),CPT-1 mRNA的表达下降(P<0.05);低、中、高剂量葱白组及易善复组肝脂肪变性减轻,舌像评分、肝指数、血浆黏度和全血黏度以及血清AST、ALT、TC、TG水平降低(P<0.05),以高剂量葱白组和易善复组下降明显,高剂量葱白组和易善复组差异无统计学意义(P> 0.05)。结论:葱白提取物治疗NAFLD有效,其机制与促进CPT-1表达及降低ACCase表达有关。
Objective:To explore the possible mechanism of treating non-alcoholic fatty liver(NAFLD) with Bulbus Allii Fistulosi extract. Methods:Sixty rats were divided into normal group,model group,low dose Bulbus Allii Fistulosi group,medium dose Bulbus Allii Fistulosi group,high dose Bulbus Allii Fistulosi group and polyene phosphatidylcholine capsule group,10 cases in each group. Animal model was established through high-fat diet. After 10 weeks of modeling,and after the histopathological identification to determine the successful establishment of model,different doses of drugs were given for 4 weeks. HE staining of liver tissue was observed under light microscope;plasma viscosity and whole blood viscosity and serum triglyceride(TG),total cholesterol(TC),aspartate aminotransferase(AST),alanine aminotransferase(ALT) level and free fatty acid(FFA) content in liver tissue were detected. Real-time PCR was used to detect the expression of acetyl-coa carboxylase(ACCase)and carnitine palmitoyltransferase-1(CPT-1) mRNA in rat livers. Results:In the model group,the liver showed obvious fatty degeneration,tongue coating score,liver index,plasma viscosity and whole blood viscosity,serum AST,ALT,TC,TG levels significantly increased(P <0.05),ACCase m RNA expression increased(P<0.05),and the expression of CPT-1 mRNA decreased(P<0.05). In the low,medium and high doses Bulbus Allii Fistulosi groups and polyene phosphatidylcholine capsule group hepatic steatosis,tongue coating score,liver index,plasma viscosity and whole blood viscosity,serum levels of AST,ALT,TC and TG were re duced(P<0.05),especially in the high dose Bulbus Allii Fistulosi group and polyene phosphatidylcholine capsule group,but there was no significant difference between both groups(P> 0.05). Conclusion:The Bulbus Allii Fistulosi extract is effective in treating NAFLD,and the mechanism is related to the promotion of CPT-1 expression and the decrease of ACCase expression.
Objective:To explore the possible mechanism of treating non-alcoholic fatty liver(NAFLD) with Bulbus Allii Fistulosi extract. Methods:Sixty rats were divided into normal group,model group,low dose Bulbus Allii Fistulosi group,medium dose Bulbus Allii Fistulosi group,high dose Bulbus Allii Fistulosi group and polyene phosphatidylcholine capsule group,10 cases in each group. Animal model was established through high-fat diet. After 10 weeks of modeling,and after the histopathological identification to determine the successful establishment of model,different doses of drugs were given for 4 weeks. HE staining of liver tissue was observed under light microscope;plasma viscosity and whole blood viscosity and serum triglyceride(TG),total cholesterol(TC),aspartate aminotransferase(AST),alanine aminotransferase(ALT) level and free fatty acid(FFA) content in liver tissue were detected. Real-time PCR was used to detect the expression of acetyl-coa carboxylase(ACCase)and carnitine palmitoyltransferase-1(CPT-1) mRNA in rat livers. Results:In the model group,the liver showed obvious fatty degeneration,tongue coating score,liver index,plasma viscosity and whole blood viscosity,serum AST,ALT,TC,TG levels significantly increased(P <0.05),ACCase m RNA expression increased(P<0.05),and the expression of CPT-1 mRNA decreased(P<0.05). In the low,medium and high doses Bulbus Allii Fistulosi groups and polyene phosphatidylcholine capsule group hepatic steatosis,tongue coating score,liver index,plasma viscosity and whole blood viscosity,serum levels of AST,ALT,TC and TG were re duced(P<0.05),especially in the high dose Bulbus Allii Fistulosi group and polyene phosphatidylcholine capsule group,but there was no significant difference between both groups(P> 0.05). Conclusion:The Bulbus Allii Fistulosi extract is effective in treating NAFLD,and the mechanism is related to the promotion of CPT-1 expression and the decrease of ACCase expression.
引文
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[6]武俊紫,贾亚敏,沈平瑞,等.富硒灵芝调控大鼠乙酰辅酶A羧化酶α表达治疗NAFLD的研究[J].天然产物研究与开发,2014,26(7):1086-1092.
[7]李红山,冯琴,胡义扬,等.祛湿化瘀方改善脂肪肝大鼠游离脂肪酸代谢的机制[J].中医杂志,2010,51(3):262-264.
[8]李红山,陈少东,应豪,等.红景天苷对高脂饮食诱导的大鼠非酒精性脂肪肝肝脏脂肪合成和氧化环节的干预作用[J].中华中医药杂志,2017(10):4625-4628.
[9]BARANOVA A,TRAN T P,BIRERDINC A,et al.Systematic review:association of polycystic ovary syndrome with metabolic syndrome and non-alcoholic fatty liver disease[J].Alimentary Pharmacology&Therapeutics,2011,33(7):801-814.
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[11]DOH K O,KIM Y W,PARK S Y,et al.Interrelation between long-chain fatty acid oxidation rate and carnitine palmitoyltransferase 1 activity with different isoforms in rat tissues[J].Life Sciences,2005,77(4):435-443.
[12]JI C,DAI Y,JIANG W,et al.Postnatal overfeeding promotes early onset and exaggeration of high-fat diet-induced nonalcoholic fatty liver disease through disordered hepatic lipid metabolism in rats[J].Journal of Nutritional Biochemistry,2014,25(11):1108-1116.
[13]郑乃汭,张优敬,吴东栋,等.硫化氢对肥胖小鼠肝脂质蓄积的影响[J].中国药理学通报,2015(7):945-951.
[14]李洁琼,郑世学,喻子牛,等.乙酰辅酶A羧化酶:脂肪酸代谢的关键酶及其基因克隆研究进展[J].应用与环境生物学报,2011,17(5):753-758.
[15]LEE J H,JUNG I R,CHOI S E,et al.Toxicity generated through inhibition of pyruvate carboxylase and carnitine palmitoyl transferase-1 is similar to high glucose/palmitate-induced glucolipotoxicity in INS-1 beta cells[J].Molecular&Cellular Endocrinology,2014,383(2):48-59.
[16]张声生,李军祥.非酒精性脂肪性肝病中医诊疗专家共识意见(2017)[J].中医杂志,2017,58(19):1706-1710.
[2]FAN J G,FARRELL G C.Epidemiology of non-alcoholic fatty liver disease in China.[J].Journal of Hepatology,2009,50(1):204-210.
[3]MASARONE M,FEDERICO A,ABENAVOLI L,et al.Non alcoholic fatty liver:epidemiology and natural history[J].Rev Recent Clin Trials,2014,9(3):126-133.
[4]冯云霞,朱旭,张介眉,等.葱白提取物对高脂血症大鼠脂质代谢的影响[J].华南国防医学杂志,2016(9):560-562.
[5]时昭红,王湘宁,张长弓,等.葱白提取物对非酒精性脂肪肝大鼠的治疗作用[J].世界华人消化杂志,2010(27):2863-2868.
[6]武俊紫,贾亚敏,沈平瑞,等.富硒灵芝调控大鼠乙酰辅酶A羧化酶α表达治疗NAFLD的研究[J].天然产物研究与开发,2014,26(7):1086-1092.
[7]李红山,冯琴,胡义扬,等.祛湿化瘀方改善脂肪肝大鼠游离脂肪酸代谢的机制[J].中医杂志,2010,51(3):262-264.
[8]李红山,陈少东,应豪,等.红景天苷对高脂饮食诱导的大鼠非酒精性脂肪肝肝脏脂肪合成和氧化环节的干预作用[J].中华中医药杂志,2017(10):4625-4628.
[9]BARANOVA A,TRAN T P,BIRERDINC A,et al.Systematic review:association of polycystic ovary syndrome with metabolic syndrome and non-alcoholic fatty liver disease[J].Alimentary Pharmacology&Therapeutics,2011,33(7):801-814.
[10]MCGARRY J D,BROWN N F.The Mitochondrial carnitine palmitoyltransferase system-from concept to molecular analysis[J].Febs Journal,2010,244(1):1-14.
[11]DOH K O,KIM Y W,PARK S Y,et al.Interrelation between long-chain fatty acid oxidation rate and carnitine palmitoyltransferase 1 activity with different isoforms in rat tissues[J].Life Sciences,2005,77(4):435-443.
[12]JI C,DAI Y,JIANG W,et al.Postnatal overfeeding promotes early onset and exaggeration of high-fat diet-induced nonalcoholic fatty liver disease through disordered hepatic lipid metabolism in rats[J].Journal of Nutritional Biochemistry,2014,25(11):1108-1116.
[13]郑乃汭,张优敬,吴东栋,等.硫化氢对肥胖小鼠肝脂质蓄积的影响[J].中国药理学通报,2015(7):945-951.
[14]李洁琼,郑世学,喻子牛,等.乙酰辅酶A羧化酶:脂肪酸代谢的关键酶及其基因克隆研究进展[J].应用与环境生物学报,2011,17(5):753-758.
[15]LEE J H,JUNG I R,CHOI S E,et al.Toxicity generated through inhibition of pyruvate carboxylase and carnitine palmitoyl transferase-1 is similar to high glucose/palmitate-induced glucolipotoxicity in INS-1 beta cells[J].Molecular&Cellular Endocrinology,2014,383(2):48-59.
[16]张声生,李军祥.非酒精性脂肪性肝病中医诊疗专家共识意见(2017)[J].中医杂志,2017,58(19):1706-1710.