骨髓间充质干细胞治疗小鼠自身免疫性肝炎  

Mice autoimmune hepatitis treated by bone marrow mesenchymal stem cell

作　　者：陈楠[1] 刘应莉[1] 刘文天[1] 王邦茂[1] 孙朝侠[2] 王玫[2] 韩明哲[2] 

机构地区：[1]天津医科大学总医院消化内科,300052 [2]中国医学科学院血液病研究所

出　　处：《中华消化杂志》2013年第1期23-27,共5页Chinese Journal of Digestion

基　　金：天津医科大学校级重点学科基金（2009XK37）

摘　　要：目的探讨骨髓间充质干细胞（MSC）移植对小鼠自身免疫性肝炎（AIH）的治疗作用及机制。方法采用C57BL／6小鼠肝特异性抗原S-100与弗氏完全佐剂诱导同种系44只小鼠建立AIH模型。造模后取6只小鼠验证AIH模型，余38只分为3组，MSC移植组（A组）14只进行MsC尾静脉注射治疗，地塞米松（DXM）治疗组（B组）12只予DXM腹腔注射治疗，PBS对照组（c组）12只予腹腔注射PBS。健康对照组（D组）18只未造模未予任何处理。于实验第5、9周测小鼠体质量，测血清ALT水平，处死各组小鼠取肝组织进行病理学检查并行肝脏炎症活动度Knodell评分，分离小鼠脾脏T淋巴细胞行增殖抑制实验。统计学分析采用秩和检验、方差分析和t检验。结果A、B组小鼠治疗后体质量均呈上升趋势（F=15．678，P〈0．01；F=3．730，P=0．037），C组治疗前后变化差异无统计学意义（P〉0．05）。实验第5、9周，A、B组小鼠血清ALT水平逐渐下降，各时间点比较差异有统计学意义（F=20．267，P〈0．01；F=4．277，P=0．034）；C组小鼠血清ALT水平治疗前后变化差异无统计学意义（P〉0．05）。实验第5、9周，A组小鼠血清ALT降低程度大于B组，差异均有统计学意义（t=3．566、3．218，P均〈0．05）。实验第5、9周，A、B组小鼠Knodell评分逐渐下降，各时间点比较差异有统计学意义（F=8．070，P=0．003；F=6．547，P=0．009）；C组小鼠Knodell评分治疗前后变化差异无统计学意义（P〉0．05）。实验第9周时，A、B、C三组小鼠Knodell评分间差异有统计学意义（F=4．477，P=0．029）。体外脾淋巴细胞增殖抑制实验显示，MSC培养上清液能显著抑制S-100抗原和刀豆蛋白A刺激的T淋巴细胞增殖，吸光度值分别为0．267±0．167比0．217±0．128和O．165±0．187比0．082±0．051，差异均有统计学意义（t=7．187、4．602，P均〈0．01）。结论MSC移植可能通Objective To explore the therapeutic effects and mechanism of bone marrow mesenchymal stem cells （MSC） transplantation in mice autoimmune hepatitis （AIH）. Methods AIH model was established in 44 C57BL/6 mice, which were induced by homologous series liver-specific antigen S-100 and Freund＇s complete adjuvant. After modeling, six mice were collected for AIH model confirming. The other 38 mice were divided into three groups. Fourteen mice of MSC transplantation group （group A） were treated by MSC tail vein injection, 12 mice of dexamethasone （DXM） group （group B） were treated by DXM intraperitoneal injection, and 12 mice of PBS control group （group C） received phosphate buffer saline （PBS） intraperitoneal injection. Eighteen mice of healthy control group （group D） weren＇t modeled and received no treatment. At the 5th and 9th week, the mice weights and serum alanine aminotransferase （ALT） level were tested, mice liver tissues of each group were estimated by pathological examination and Knodell scoring, and spleen T lymphocytes of mice were isolated for proliferation-inhibition examination. The data were analyzed by rank sum test, ANOVA and t test. Results After treatment, mice weights of both group A and B showed upward trend （F=15. 678, P〈0. 01; F=3. 730, P=0. 037）. Before and after treatment, there was no significant difference in group C （P〉0.05）. At the 5th and 9th week, the ALT level of group A and B gradually decreased, there was statistical significance between the time points （F=20. 267, P〈0.01; F=4. 277, P=0. 034）. Before and after treatment, there was no significant difference in ALT level of group C （P〉0.05）. At the 5th and 9th week, the degree of mice serum ALT reduction of group A was larger than that of group B, and the difference was statistically significant （t= 3. 566 and 3. 218, both P〈0.05）. At the 5th and 9th week, the Kondell scores of group A and B gradually decreased, there was statistical significance between the time points

关 键 词：骨髓移植 间充质干细胞移植 肝炎 自身免疫性 T淋巴细胞 小鼠 近交C57BL 

分 类 号：R575.1[医药卫生—消化系统]