Mice autoimmune hepatitis treated by bone marrow mesenchymal stem cell / 中华消化杂志

ABSTRACT

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 (F=8.070,P=0.003; F=6.547,P=0.009).Before and after treatment,there was no significant difference in Kondell scores of group C (P＞0.05).At the 9th week,there was statistical significance in Kondell scores among group A,group B and group C (F =4.477,P =0.029).The in vitro spleen lymphocytes proliferation-inhibition experiment demonstrated that the supernatant of MSC could significantly inhibit the proliferation of T lymphocytes stimulated by S-100 antigen and concanavalin A,the absorbance values were0.267±0.167 vs.0.217±0.128 and0.165±0.187 vs.0.082±0.051 respectively,the differences were statistically significant (t =7.187 and 4.602,both P＜ 0.01).Conclusion MSC transplantation may play a therapeutic role in mice AIH through inhibiting T lymphocyte proliferation.