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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
引用本文: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. 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[J]. 临床肝胆病杂志, 2019, 35(3): 592-595
作者姓名: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
作者单位: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,北京100069;济宁医学院附属医院消化内科,山东济宁,272000;济宁医学院免疫学与分子医学研究所,山东济宁,272000;济宁医学院附属医院肝病研究所,山东济宁,272000;济宁医学院附属医院神经内科,山东济宁,272000;济宁医学院附属医院病理科,山东济宁,272000;上海美峰生物技术有限公司,上海,201203
基金项目:国家科技重大专项;国家科技重大专项;国家科技重大专项;国家科技重大专项;国家科技重大专项;国家重点研发计划;国家自然科学基金;国家自然科学基金
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,差异均有统计学意义(P值均<0.05);肝脏HE染色和油红O染色均显示S组小鼠的肝脏脂肪变性程度较M组明显减轻。结论 腹腔肝源性干细胞移植对小鼠酒精性脂肪肝具有显著的防治作用。

关 键 词:脂肪肝,酒精性  干细胞移植  小鼠,近交C57BL

Effect of human liver-derived stem cells in prevention and treatment of alcoholic fatty liver disease in mice
Affiliation:(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, Beijing 100069, China)
Abstract:ObjectiveTo 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 C57BL/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. ConclusionIntraperitoneal transplantation of human liver-derived stem cells has a marked effect in the prevention and treatment of alcoholic fatty liver disease in mice.
Keywords:fatty liver, alcoholic  stem cell transplantation  mice, inbred C57BL
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