人脐带间充质干细胞对CCl_4致大鼠肝硬化的保护作用研究

Protective Effect of Human Umbilical Cord Mesenchymal Stem Cell on Hepatocirrhosis Rats Induced by CCl_4

目的:研究人脐带间充质干细胞(HUC-MSCs)对CCl4致大鼠肝硬化的保护作用及其机制。方法:对大鼠皮下注射CCl4建立肝硬化模型,并于造模成功后继续半剂量注射CCl4,建模成功后随机分为模型组、生理盐水(NS)组、HUC-MSCs组(1×107个/mL),每组24只,后2组通过尾静脉注射,移植相应药物或细胞1mL,移植后第1、3、5周末观察各组大鼠肝组织病理学变化及其血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、胆固醇(CHO)、白蛋白(ALB)、转化生长因子β(1TGF-β1)、肝细胞生长因子(HGF)水平和肝组织中人表皮生长因子受体(EGF-R)的表达情况;另选取8只正常大鼠设为正常对照组。结果:模型组和NS组相似,大鼠肝内胶原纤维增生明显,肝细胞排列紊乱,HUC-MSCs组移植后5周大鼠的肝内胶原纤维增生减少,有较多正常肝细胞;与正常对照组比较,模型组和NS组大鼠的ALT、AST、TGF-β1、HGF水平均明显升高,CHO、ALB含量明显降低(P<0.01);与模型组比较,HUC-MSCs组上述指标均明显好转(P<0.05或P<0.01),其中ALT、ALB、TGF-β1水平与移植后的时间呈正相关;HUC-MSCs组移植后1、3、5周大鼠肝组织中均有人EGF-R的阳性表达。结论:HUC-MSCs可促进肝功能的改善,修复肝硬化损伤的肝脏组织。

OBJECTIVE： To investigate the protective effect of human umbilical cord mesenchymal stem cells （HUC-MSCs） on hepatocirrhosis in rats and its mechanism. METHODS： Rats hepatocirrhosis model was induced by subcutaneous injection of CCl4. Model rats were given half dose of CCL continuously after modeling. The experimental animals were randomly divided into model group, normal saline （NS） group and HUC-MSCs group （1×107 counts/mL） with 24 rats in each group. The latter 2 groups were given intravenous injection of drug or cell 1 mL via tail vein. After transplantation, respectively at the 1st, 3rd, 5th weekend rats were sacrificed for detecting pathological changes of liver tissue, the levels of ALT, AST, CHO, ALB, TGF-β1, HGF and EGF-R. Other 8 rats were involved in normal control group. RESULTS： There was similar condition in model group and NS group. Collagen fibre proliferated obviously in liver, and liver cell disarranged. In HUC-MSCs group, 5 weeks after transplantation the proliferation of collagen fibre in liver decreased and there were many normal liver cell; compared with normal control group, ALT, AST, TGF-β1 and HGF levels increased significantly in model group and NS group, and the contents of CHO and ALB decreased significantly （P〈0.01）. Compared with model group, above parameters of HUC-MSCs group improved significantly （P〈0.05 or P〈 0.01） ; ALT, ALB and TGF-β1 levels were positively correlated with time after transplantation. The positive expression of human EGF-R was found in liver tissue of rats in HUC-MSCs group at 1, 3, 5 weeks after transplantation. CONCLUSION： HUC-MSCs transplantation can promote the repair of liver function and repair liver lesions induced by hepatocirrhosis.