人脐带源间充质干细胞移植改善四氯化碳诱导肝硬化大鼠的肝纤维化

Transplantation of human umbilical cord-derived mesenchymal stem cells improves hepatic fibrosis in rats with carbon etrachloride-induced hepatic cirrhosis

背景:干细胞移植作为一种全新的肝硬化治疗方法的可行性和有效性,在国内外文献中报道极少。目的:观察人脐带源间充质干细胞移植对四氯化碳诱导肝硬化大鼠肝纤维化的影响。方法:32只Wistar大鼠随机分为2组,对照组经尾静脉内注射生理盐水,肝硬化组采用四氯化碳植物油皮下注射8周制成肝硬化大鼠模型,再随机分为3组,盐水对照组、人脐带源间充质干细胞移植组分别经尾静脉内注射生理盐水和人脐带源间充质干细胞混悬液,8周肝硬化组无其他干预。结果与结论:对照组血清碱性磷酸酶水平明显低于其他3组(P<0.05);人脐带源间充质干细胞移植组血清白蛋白和胆固醇水平与对照鼠相近(P>0.05),与8周肝硬化组和盐水对照组相比明显升高(P<0.05)。血清碱性磷酸酶水平也出现了明显下降(P<0.05)。肝硬化8周组大鼠肝组织中有大量胶原纤维增生并形成假小叶;盐水对照组与肝硬化8周组相似;仅在人脐带源间充质干细胞移植组大鼠肝中观察到散在的绿色抗人抗核抗体阳性细胞,肝组织中胶原纤维的量明显小于盐水对照组。提示经尾静脉移植人脐带源间充质干细胞,可明显改善四氯化碳诱导肝硬化大鼠的肝纤维化程度。

BACKGROUND：The feasibility and efficacy of stem cell transplantation as a new method in treatment of hepatic cirrhosis have been rarely reported at home and abroad.OBJECTIVE：To investigate the effects of human umbilical cord-derived mesenchymal stem cells（hUCMSCs） on hepatic fibrosis in rats with carbon etrachloride-induced hepatic cirrhosis.METHODS：Thirty-two Wistar rats were randomly divided into two groups.Rats in the control group were injected with normal saline via the tail vein.Rats in the hepatic cirrhosis group were established into rat models of hepatic cirrhosis by cutaneous injection of carbon etrachloride peanut oil for 8 weeks.The hepatic cirrhosis rats were then randomly sub-divided into three groups：8-week hepatic cirrhosis,normal saline,hUCMSCs transplantation.Rats in the normal saline and hUCMSCs transplantation subgroups were administered normal saline and hUCMSCs suspension respectively via the tail vein.Rats in the 8-week hepatic cirrhosis received no intervention.RESULTS AND CONCLUSION：Serum alkaline phosphatase level was significantly lower in the control group than in the other three subgroups（P 0.05）.Serum albumin and cholesterol levels in the hUCMSCs group were similar to those of control group（P 0.05）,but they were significantly higher compared with 8-week hepatic cirrhosis and normal saline group（P 0.05）.In the 8-week hepatic cirrhosis group,a large amount of hyperplastic collagenous fiber was presented in the liver tissue and the frame of the pseudolobuli formed.The normal saline group and 8-week hepatic cirrhosis group exhibited similar histological changes.Scattered green antinuclear antibody-positive cells in the liver were only observed in the hUCMSCs group.The amount of hyperplastic collagenous fiber was significantly lower in the hUCMSCs transplantation group than in the normal saline group.These findings suggest that transplantation of human umbilical cord-derived mesenchymal stem cells via the tail vein can obviously improve hepatic fibrosis in rats with carbon etrachloride-induced hepatic cirrhosis.