肝爽颗粒对新型组织工程肝脏非酒精性脂肪性肝病大鼠模型脂代谢的影响

张译之; 段钟平; 张晓慧; 陈煜

doi:10.3969/j.issn.1001-5256.2020.07.020

肝爽颗粒对新型组织工程肝脏非酒精性脂肪性肝病大鼠模型脂代谢的影响

DOI: 10.3969/j.issn.1001-5256.2020.07.020

首都医科大学附属北京佑安医院疑难肝病及人工肝中心，肝衰竭与人工肝治疗研究北京市重点实验室

基金项目:

北京市自然科学基金(7202070)；国家重点研发计划资助(2017YFA0103000)；国家科技重大专项“艾滋病和病毒性肝炎等重大传染病防治”(2017ZX10203201-005,2017ZX10201201-001-001,2017ZX10201201-002-002,2017ZX10201201-004-002,2017ZX10202203-006-001,2017ZX10302201-004-002)；北京市医院管理局临床医学发展专项经费资助(ZYLX201806)；中国肝炎防治基金会天晴肝病研究基金(TQGB20200101)；国家自然科学基金(81500472)；

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中图分类号: R575.5
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出版历程
- 出版日期: 2020-07-20

Effect of Ganshuang granules on lipid metabolism in a new tissue-engineering model of nonalcoholic fatty liver disease

Intractable Hepatic Diseases and Artificial Liver Treatment & Training Center, Beijing YouAn Hospital, Capital Medical University；Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research; Beijing 100069, China

Research funding:

摘要

摘要: 目的探讨肝爽颗粒（GSG）干预对新型组织工程肝脏非酒精性脂肪性肝病（NAFLD）模型脂代谢的影响及其机制。方法将Sprague Dawley大鼠肝脏去细胞化制为肝脏胶原支架,用人Hep G2细胞对支架再细胞化,从而获得组织工程（TE）肝（正常对照组）,用含游离脂肪酸（FFA）的高脂培养基灌注TE肝建立NAFLD模型（FFA组）,该模型进一步用GSG浸膏处理后为FFA+GSG组。比较各组肝脏TG含量及丙酮酸脱氢酶激酶4（PDK4） mRNA水平;比较FFA组和FFA+GSG组脂代谢相关酶mRNA表达情况,并行油红O染色评估肝脏病理学。计量资料组间差异比较采用t检验。结果 FFA组TG含量较正常对照组显著升高（t=4. 842,P=0. 004 7）,FFA组PDK4 mRNA水平较正常组显著升高（t=2. 784,P=0. 031 8）; FFA+GSG组较FFA组细胞内TG水平显著下降（t=0. 055,P=0. 003 7）,PDK4表达显著降低（t=3. 761,P=0. 009 4）;脂肪酸转位酶、脂肪酸结合蛋白1、ATP柠檬酸裂解酶、乙酰辅酶A羧化酶、脂肪酸合成酶、脂肪酸去饱和...
- 非酒精性脂肪性肝病 /
- 组织工程 /
- 肝爽颗粒 /
- 大鼠,Sprague-Dawley
Abstract: Objective To investigate the effect of Ganshuang granules( GSG) intervention on lipid metabolism in a new tissue-engineering model of nonalcoholic fatty liver disease( NAFLD) and its mechanism. Methods The liver of Sprague-Dawley rats was decellularized into collagen scaffolds,and human HepG2 cells were used to recellularize the scaffolds to obtain the tissue-engineering( TE) liver as normal control group. The TE liver was perfused with high-fat medium containing free fatty acid( FFA) to establish a model of NAFLD( FFA group),and this model was further treated with GSG extract to establish a FFA + GSG group. These groups were compared in terms of the content of triglyceride( TG) and the mRNA expression of PDK4 in the liver,and the mRNA expression of enzymes associated with lipid metabolism was compared between the FFA group and the FFA + GSG group; oil red O staining was used to evaluate liver pathology. The t-test was used for comparison of continuous data between groups. Results Compared with the normal control group,the FFA group had significantly higher content of TG( t = 4. 842,P = 0. 004 7) and mRNA expression of PDK4( t = 2. 784,P = 0. 031 8). Compared with the FFA group,the FFA + GSG group had significant reductions in the content of TG in cells( t = 0. 055,P = 0. 003 7),the expression of PDK4( t = 3. 761,P = 0. 009 4),and the mRNA expression of fatty acid translocase,fatty acid-binding protein 1,ATP citrate lyase,acetyl-CoA carboxylase,fatty acid synthase,fatty acid desaturase 2,1-acylglycerol-3-phosphate O-acyltransferase 5,and apolipoprotein B( t = 6. 552,4. 944,2. 689,4. 524,6. 040,3. 758,4. 443,and 3. 032,P = 0. 007 2,0. 001 1,0. 027 6,0. 020 2,0. 009 1,0. 005 6,0. 047 1,and 0. 016 3). Oil red O staining showed significant reductions in the number of lipid droplets in hepatocytes and the degree of hepatocyte fatty degeneration. Conclusion GSG can reduce the intake of FFA,the de novo synthesis of fatty acid,and the generation and deposition of TG in hepatocytes in the model of NAFLD and thus improve dyslipidemia.
- nonalcoholic fatty liver disease /
- tissue engineering /
- Ganshuang granule /
- rats,Sprague-Dawley

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参考文献(25)

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