人成体肝源性干细胞对酒精性脂肪肝小鼠模型的防治作用

毕研贞; 张秋生; 樊增; 杨永红; 张小蓓; 王全全; 王全义; 王一波; 段钟平; 陈煜; 舒振锋; 司传平; 洪丰

doi:10.3969/j.issn.1001-5256.2019.03.027

人成体肝源性干细胞对酒精性脂肪肝小鼠模型的防治作用

DOI: 10.3969/j.issn.1001-5256.2019.03.027

1. 首都医科大学附属北京佑安医院疑难肝病及人工肝中心,肝衰竭及人工肝治疗研究北京市重点实验室
2. 济宁医学院附属医院消化内科
3. 济宁医学院免疫学与分子医学研究所
4. 济宁医学院附属医院肝病研究所
5. 济宁医学院附属医院神经内科
6. 济宁医学院附属医院病理科

基金项目:

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”(2017ZX10203201-005,2017ZX10202203-006-001,2017ZX10302201-004-002,2012ZX10002004-006,2017ZX10201201)；国家重点研发计划(2017YFA0103000)；国家自然科学基金(81170395,81570556)；

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中图分类号: R575.5;R-332
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出版历程
- 出版日期: 2019-03-20

Effect of human liver-derived stem cells in prevention and treatment of alcoholic fatty liver disease in mice

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

Research funding:

摘要

摘要:
目的探讨人肝源性干细胞腹腔移植对小鼠酒精性脂肪肝的防治作用。方法将30只雄性C57BL/6小鼠随机分为空白对照组（N组）、模型对照组（M组）以及肝干细胞移植组（S组）。N组以基础饲料喂养,M组和S组以Lieber-DeCarli酒精液体饲料喂养,S组每周进行2次腹腔肝干细胞移植。干预6周后,测定各组小鼠体质量、肝脏指数,检测血清ALT、AST、TBil、TC、TG、HDL-C、LDL-C,检测肝脏中TG和游离脂肪酸（NEFA）水平,并做肝脏病理学检查和肝组织油红O染色。计量资料多组间比较采用单因素方差分析,进一步两两比较采用SNK-q检验。结果 3组间比较,小鼠血清ALT、AST、TG、TC、HDL-C水平和肝组织TG、NEFA水平差异均具有统计学意义（F值分别为66. 94、7. 15、8. 02、18. 64、3. 86、23. 14、30. 49,P值均<0. 05）。与N组对比,M组小鼠的血清中ALT、AST、TG和肝组织中TG、NEFA明显升高,差异均有统计学意义（P值均<0. 05）。S组小鼠的血清ALT、AST、TG和肝组织TG、NEFA都明显低于M组,差异均...
- 脂肪肝,酒精性 /
- 干细胞移植 /
- 小鼠,近交C57BL
Abstract:
Objective To investigate the effect of intraperitoneal transplantation of human liver-derived stem cells in the prevention and treatment of alcoholic fatty liver disease in mice. Methods A total of 30 male C57 BL/6 mice were randomly divided into blank control group ( group N) , model control group ( group M) , and stem cell transplantation group ( group S) . The mice in group N were fed a normal diet, and those in the other two groups were fed Lieber-DeCarli alcohol liquid diet; at the same time, the mice in group S were given intraperitoneal transplantation of human liver-derived stem cells twice a week. After six weeks of intervention, body weight and liver index were measured, and the serum levels of alanine aminotransferase ( ALT) , aspartate aminotransferase ( AST) , total bilirubin ( TBil) , total cholesterol ( TC) , triglyceride ( TG) , high-density lipoprotein cholesterol ( HDL-C) , and low-density lipoprotein cholesterol ( LDL-C) were also measured. The levels of TG and non-esterified fatty acid ( NEFA) in the liver were measured, and liver pathological examination and oil red O staining of the liver were performed. One-way ANOVA was used for comparison of continuous data between multiple groups, and the SNK-q test was used for further comparison between two groups. Results There were significant differences in the serum levels of ALT, AST, TG, TC, and HDL-C and the content of TG and NEFA in the liver between the three groups ( F = 66. 94, 7. 15, 8. 02, 18. 64, 3. 86, 23. 14 and 30. 49, all P < 0. 05) , Compared with group N, group M showed significant increases in levels of ALT, AST, and TG in serum and levels of TG and NEFA in liver tissue ( all P < 0. 05) . Group S had significantly lower levels of ALT, AST, and TG in serum and levels of TG and NEFA in liver tissue than group M ( all P < 0. 05) . Liver HE staining and oil red O staining showed that group S had a significantly lower degree of liver steatosis than group M. Conclusion Intraperitoneal transplantation of human liver-derived stem cells has a marked effect in the prevention and treatment of alcoholic fatty liver disease in mice.
- fatty liver, alcoholic /
- stem cell transplantation /
- mice, inbred C57BL

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参考文献(23)

[1] Fatty Liver and Alcoholic Liver Disease Study Group of the Chi-nese Liver Disease Association, Chinese Medical Association.Guidelines for prevention and treatment of alcoholic liver dis-ease (revised version 2010) [J]. J Clin Hepatol, 2010, 26 (3) :229-232. (in Chinese) 中华医学会肝病学分会脂肪肝和酒精性肝病学组.酒精性肝病诊疗指南 (2010年修订版) [J].临床肝胆病杂志, 2010, 26 (3) :229-232.

[2] European Association for the Study of Liver. EASL clinical practi-cal guidelines:Management of alcoholic liver disease[J]. J Hep-atol, 2012, 57 (2) :399-420.

[3] WARREN KR, MURRAY MM. Alcoholic liver disease and pan-creatitis:Global health problems being addressed by the USNational Institute on Alcohol Abuse and Alcoholism[J]. J Gas-troenterol Hepatol, 2013, 28 (Suppl 1) :4-6.

[4] O'SHEA RS, DASARATHY S, MCCULLOUGH AJ. Alcoholicliver disease[J]. Hepatology, 2010, 51 (1) :307-328.

[5] MCCULLOUGH AJ, O'SHEA RS, DASARATHY S. Diagnosisand management of alcoholic liver disease[J]. J Dig Dis, 2011, 12 (4) :257-262.

[6] FAN JG. Epidemiology of alcoholic and nonalcoholic fatty liverdisease in China[J]. J Gastroenterol Hepatol, 2013, 28 (Sup-pl 1) :11-17.

[7] AKIYAMA K, CHEN C, WANG D, et al. Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis[J]. Cell Stem Cell, 2012, 10 (5) :544-555.

[8] KUO TK, HUNG SP, CHUANG CH, et al. Stem cell therapyfor liver disease:Parameters governing the success of usingbone marrow mesenchymal stem cells[J]. Gastroenterology, 2008, 134 (7) :2111-2121.

[9] ZHANG Z, WANG FS. Stem cell therapies for liver failure andcirrhosis[J]. J Hepatol, 2013, 59 (1) :183-185.

[10] SPAHR L, LAMBERT JF, RUBBIA-BRANDT L, et al. Granu-locyte-colony stimulating factor induces proliferation of hepat-ic progenitors in alcoholic steatohepatitis:A randomized trial[J]. Hepatology, 2008, 48 (1) :221-229

[11] AURICH H, SGODDA M, KALTWASSER P, et al. Hepatocytedifferentiation of mesenchymal stem cells from human adiposetissue in vitro promotes hepatic integration in vivo[J]. Gut, 2009, 58 (4) :570-581.

[12] BI YZ, FAN Z, CHEN DF, et al. Protective effect of intraperito-neal transplantation of human fiver-derived stem cells at dif-ferent times against concanavalin A-induced acute liver injuryin mice[J]. Chin J Hepatol, 2017, 25 (3) :205-210. (inChinese) 毕研贞, 樊增, 陈东风, 等.人肝源性干细胞腹腔移植不同时间对Con A诱导小鼠急性肝损伤保护作用[J].中华肝脏病杂志, 2017, 25 (3) :205-210.

[13] LOMBARD R, BUZZETTI E, ROCCARINA D, et al. Non-in-vasive assessment of liver fibrosis in patients with alcoholic liv-er disease[J]. World J Gastroenterol, 2015, 21 (39) :11044-11052.

[14] MANDAL A, GRUPP A, SCHWEDERSKI B, et al. Noninno-cently behaving bridging anions of the widely distributed an-tioxidant ellagic acid in diruthenium complexes[J]. InorgChem, 2015, 54 (20) :10049-10057.

[15] LIN XX, CHEN D, ZHAO Q, et al. Genetic research on the in-cidence of alcoholic liver disease[J]. Chin J Clin PharmacolTher, 2017, 22 (11) :1309-1314. (in Chinese) 林秀贤, 陈丹, 赵青, 等.影响酒精性肝病发病的遗传学研究进展[J].中国临床药理学与治疗学, 2017, 22 (11) :1309-1314.

[16] SZABO G. Gut-liver axis in alcoholic liver disease[J]. Gas-troenterology, 2015, 148 (1) :30-36.

[17] DI CAMPLI C, PISCAGLI AC, PIERELLI L, et al. A human um-bilical cord stem cell rescue therapy in a murine model of toxicliver injury[J]. Dig Liver Dis, 2004, 36 (9) :603-613.

[18] YANG S, KOTEISH A, LIN H, et al. Oval cells compensate fordamage and replicative senescence of mature hepatocytes inmice with fatty liver disease[J]. Hepatology, 2004, 39 (2) :403-411.

[19] MARGINI C, VUKOTIC R, BRODOSI L, et al. Bone marrowderived stem cells for the treatment of end-stage liver dis-ease[J]. World J Gastroenterol, 2014, 20 (27) :9098-9105.

[20] CHEN Q, KHOURY M, LIMMON G, et al. Human fetal hepaticprogenitor cells are distinct from, but closely related to, hema-topoietic stem/progenitor cells[J]. Stem Cells, 2013, 31 (6) :1160-1169.

[21] PICHARD V, FERRY N. Origin of small hepatocyte-like pro-genitor in retrorsine-treated rats[J]. J Hepatol, 2008, 48 (2) :368-369.

[22] GERBAL-CHALOIN S, FUNAKOSHI N, CAILLAUD A, et al.Human induced pluripotent stem cells in hepatology:Beyondthe proof of concept[J]. Am J Pathol, 2014, 184 (2) :332-347.

[23] ENOSAWA S, HORIKAWA R, YAMAMOTO A, et al. Hepato-cyte transplantation using a living donor reduced graft in a ba-by with ornithine transcarbamylase deficiency:A novel sourceof hepatocytes[J]. Liver Tranpl, 2014, 20 (3) :391-393.

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