骨髓间充质干细胞对原发性胆汁性肝硬化动物模型治疗作用研究初探

Preliminary study of bone marrow derived mesenchymal stem cell transplantation for primary blliary cirrhosis of animal models

目的探讨骨髓间充质干细胞（BM—MSC）对原发性胆汁性肝硬化（PBC）动物模型的治疗作用。方法23只C57BL／6小鼠随机分为对照组（4只）和模型组（19只），模型组以聚肌苷酸胞苷酸（Poly I：C）每周2次腹腔注射，对照组以磷酸盐缓冲液（PBS）代替Poly I：C，16周后模型组小鼠随机取4只，对照组小鼠全部处死，观察造模情况。随后模型组小鼠随机分为BM—MSC治疗组（8只）和未治疗组（7只），6周后所有小鼠处死，观察移植疗效。结果①Poly I：C诱导16周后，模型组小鼠丙氨酸转氨酶（ALT）、碱性磷酸酶（ALP）均升高，其中ALP水平显著升高（P〈0．05）。模型组小鼠均出现血清抗线粒体抗体（AMA）高滴度阳性，抗核抗体（ANA）不同滴度阳性，肝脏汇管区大量炎症细胞浸润。②6周后，BM-MSC治疗组和未治疗组ALP显著下降[（112±16）和（135±16）U／L，P=0．01]，ALT水平[（30．1±5．9）U／L]也下降，但与未治疗组相比[（34．9±2．5）U／L]，差异无统计学意义（P〉0．05）。③MSC治疗组小鼠血清AMA滴度显著低于未治疗组（P〈0．05），ANA滴度也有下降（P〉0．05）。④MSC移植能显著改善PBC模型鼠肝脏炎症细胞浸润。结论Poly I：C腹腔注射能建立较为稳定的PBC模型，BM—MSC移植对PBC动物模型有治疗作用。

Objective To investigate the therapeutic effect of bone marrow mesenchmal stem cell （BM-MSC） transplantation for primary biliary cirrhosis （PBC） in animal models induced by polyinosinic polycytidylic acid （Poly I：C）. Methods Twenty three 4-6 week old C57BL/6 mice were divided into two groups as following： mice in model group were injected with Poly I：C intraperitoneally two times per week, and the control group were treated with PBS instead. PBC animal models were established 16 weeks after the injection. Then the mice in the PBC models were divided into BM-MSC-treated group and no BM-MSC group, all mice were sacrificed 6 weeks later in order to test the therapeutic effect of BM-MSC. Results （1） Sixteen weeks after Poly I：C injection, mice in the model group had much higher level of ALP than the control group （P〈0.05）, ALT level was also increased, and the positive rate of AMA and ANA was elevated at different extent. Infiltration of mononuclear cells was observed in the portal area in the livers of the model group. （2） After 6 weeks of BM-MSC injection, ALP levels＇ decreased significantly [ （ 112± 16） U/L vs （ 135± 16） U/L, P= 0.01 ]. ALT level was also decreased, but with no significant difference （P〉0.05）. （3） The titer of AMA and ANA in BM-MSC-treated group was much lower than that of the no BM-MSC group after 6 weeks （P〈0.05）. （4）BM-MSC treatment could ameliorate the histological changes of liver in PBC mice. Conclusion Animal models of PBC can be established by injection of Poly I：C. BM-MSC transplantation has therapeutic effect on PBC animal models.