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目的研究人间充质干细胞(MSCs)移植对四氯化碳诱导性肝硬化大鼠肝纤维化的影响。方法实验动物随机分为对照组和肝硬化组,肝硬化组采用60%的四氯化碳植物油皮下注射7周制成肝硬化大鼠模型,再随机分成肝硬化7周组、MSC对照组和MSC移植组。在MSC移植组,人胚胎脐带血源的MSCs鉴定后,经肠系膜上静脉注射移植入大鼠体内,3周后处死所有大鼠,行肝组织冰冻切片,抗人表皮生长因子受体(EGF-R)的免疫组织化学显色和天狼猩红染色。结果肝硬化7周组、MSC对照组和MSC移植组大鼠的血清碱性磷酸酶白蛋白(ALP)(、ALB)和胆固醇(CHO)含量出现了不同程度的异常。肝硬化7周组大鼠肝组织中有大量的胶原纤维增生并形成假小叶;MSC对白蛋白照组与肝硬化7周组相似;仅在MSC移植组的大鼠肝中观察到散在的棕黄色的抗人EGF-R阳性细胞,肝组织中胶原纤维的量明显小于MSC对照组。结论经肠系膜上静脉移植人MSC,可明显改善四氯化碳诱导性肝硬化大鼠的肝纤维化程度,为肝硬化的治疗提供实验依据。
Objective To investigate the effects of human mesenchymal stem cells (MSCs) transplantation on hepatic fibrosis induced by carbon tetrachloride-induced cirrhosis in rats. Methods The experimental animals were randomly divided into control group and cirrhosis group. Liver cirrhosis group was induced by subcutaneous injection of 60% carbon tetrachloride vegetable oil for 7 weeks and then randomly divided into hepatic cirrhosis 7 week group, MSC control group and MSC transplantation group. In MSCs transplanted group, MSCs were identified from cord blood of human embryos, then transplanted into the rats via superior mesenteric vein. After 3 weeks, all the rats were sacrificed, frozen sections of liver tissue were harvested, and anti-human epidermal growth factor receptor (EGF- R) immunohistochemical staining and Sirius red staining. Results Serum levels of ALP (ALB) and cholesterol (CHO) in cirrhotic rats at 7 weeks, MSC and MSC groups showed different degrees of abnormalities. A large number of collagen fibers hyperplasia and pseudolobules were formed in the hepatic tissue of cirrhotic rats for 7 weeks. MSC and albumin groups were similar to those of cirrhosis for 7 weeks. Scattered brownish yellow Of anti-human EGF-R positive cells, the amount of collagen fibers in liver tissue was significantly smaller than the MSC control group. Conclusion Transplantation of human MSC through the superior mesenteric vein can significantly improve the degree of liver fibrosis induced by carbon tetrachloride-induced cirrhosis in rats and provide an experimental basis for the treatment of cirrhosis.