骨髓间充质干细胞经尾静脉移植治疗肝纤维化

Bone marrow mesenchymal stem cell transplantation via the tail vein for liver fibrosis

背景：肝纤维化是终末肝病的早期阶段,对肝纤维化进行有效治疗可以防止终末肝病的发生,骨髓间充质干细胞是治疗肝纤维化的一种比较有前景的治疗方法。目的：探讨骨髓间充质干细胞对大鼠肝纤维化的治疗作用。方法：将18只SD大鼠随机分为3组,对照组、模型组和移植组。模型组和移植组应用四氯化碳诱导建立大鼠肝纤维化模型,造模后移植组大鼠经尾静脉缓慢注入1 mL骨髓间充质干细胞（5×10^5个）,模型组经尾静脉注入等量的生理盐水;对照组大鼠不予任何处理。移植治疗后4周,检测各组大鼠肝纤维化、肝功能指标,观察大鼠肝脏病理组织学变化。结果与结论：1对照组肝脏组织结构正常;模型组肝脏组织内门管区见纤维组织增生,有炎症细胞浸润,肝细胞空泡变性,排列紊乱,组织结构破坏;移植组肝脏组织破坏介于正常组和模型组之间。2移植组肝纤维化指标血清透明质酸酶、血清Ⅳ型胶原、血清Ⅲ型前胶原水平均明显低于模型组（P〈0.05）;移植组肝功能指标血清谷丙转氨酶、血清白蛋白、谷草转氨酶水平均明显低于模型组（P〈0.05）。3结果表明四氯化碳可以诱导大鼠肝纤维化,骨髓间充质干细胞移植可以减轻肝脏纤维化程度,改善肝脏功能。

BACKGROUND： Liver fibrosis is the early stage of terminal liver diseases. Effective treatment for liver fibrosis can prevent the occurrence of terminal liver diseases. Bone marrow mesenchymal stem cell transplantation is a promising method to treat liver fibrosis. OBJECTIVE： To study the therapeutic effect of bone marrow mesenchymal stem cells on liver fibrosis in rats. METHODS： Eighteen Sprague-Dawely rats were randomized into three groups： control, model and cell transplantation groups. Animal models of carbon tetrachloride-induced liver fibrosis were made in the latter two groups. After modeling, 1 mL bone marrow mesenchymal stem cells（5×10^5） or the same volume of normal saline was injected via the tail vein into the rats in the cell transplantation and model groups, respectively. Rats in the control group were given no treatment. Degree of liver fibrosis, liver function, histological changes of the liver were detected and observed in the three groups at 4 weeks after treatment. RESULTS AND CONCLUSION： In the control group, the liver tissues had normal structure with no fibrosis;in the model group, proliferation of fibrous tissues in the portal area of the liver, inflammatory cell infiltration,vacuolar degeneration and irregular arrangement of liver cells, and tissue structure damage were observed; in the transplantation group, liver tissue damage was severer than the control group but milder than the model group. Levels of serum hyaluronidase, type IV collagen and procollagen III were significantly lower in the cell transplantation group than the model group（P〈0.05）. These findings indicate that bone marrow mesenchymal stem cell transplantation can alleviate liver fibrosis and improve liver function in rats with carbon tetrachloride-induced liver fibrosis.