[关键词]
[摘要]
目的 探讨虫草多糖联合骨髓间充质干细胞(mesenchymal stem cells,MSCs)移植对四氯化碳(CCl4)诱导的肝硬化大鼠MMP-13和TIMP-1表达的影响。方法 取SD大鼠随机分成正常对照组、模型组、MSCs移植组、虫草多糖组及MSCs移植+虫草多糖组,除正常对照组外所有大鼠皮下注射40 % CCl4橄榄油溶液12周制备大鼠肝硬化模型,MSCs移植组与MSCs移植 虫草多糖组注入绿色荧光蛋白(green fluorescent protein,GFP)标记的MSCs;虫草多糖组、MSCs移植 虫草多糖组在移植后24 h给予虫草多糖悬浊液灌胃,正常对照组、模型组、MSCs移植组给予等量生理盐水灌胃,每天1次。4周末处死大鼠,取肝脏,行冰冻切片荧光检测、肝组织Masson染色、免疫组织化学法检测基质金属蛋白酶-13(MMP-13)、基质金属蛋白酶抑制因子-1(TIMP-1)表达。结果 各治疗组均能减轻肝硬化组织病理改变,减少胶原沉积;与模型组比较,各治疗组MMP-13的表达显著升高(P < 0.05),TIMP1表达下降(P < 0.05);MSCs移植 虫草多糖组与MSCs移植组和虫草多糖组比较,差异有统计学意义(P < 0.05)。结论 MSCs能迁移定植于受损肝脏,虫草多糖联合MSCs移植能降低肝组织TIMP-1表达,进一步增强MMP-13表达,明显促进胶原降解,减少胶原沉积。
[Key word]
[Abstract]
Objective To observe the effects of Cordyceps polysaccharide combined with mesenchymal stem cells(MSCs) transplantation on the expression of matrix metalloproteinase 13(MMP-13) and tissue inhibitor of metalloproteinase 1(TIMP-1) in rats with carbon tetrachloride induced liver cirrhosis. Methods SD rats were randomly divided into 5 groups,namely normal group,model control group,MSCs transplantation group,Cordyceps polysaccharide group and combination group(treated with MSCs transplantation+Cordyceps polysaccharide). Except for the normal group,rats in other groups were given subcutaneous injection of carbon tetrachloride for 12 weeks to induce liver cirrhosis. MSCs transplantation group and the combination group separately were injected MSCs labeled by green fluorescent protein(GFP). Cordyceps polysaccharide group and the combination group were given intragastric infusion of Cordyceps polysaccharide 24 h after MSCs transplantation. Normal group,model control group and MSCs transplantation group were given isodose normal saline once per day. At the end of the 4 th week,all rats were executed and liver tissue were prepared into frozen section. Fluorescence detection,Masson staining,and immunohistochemical detection were carried out for measuring MMP-13 and TIMP-1 expression. Results The pathological changes of liver cirrhosis were alleviated and collagen deposition was reduced in each medication group. Compared with the model group,the MMP-13 expression of medication groups was significantly increased(P < 0.05),and TIMP-1 expression was significantly decreased(P < 0.05). There were significant difference between the combination group and MSCs transplantation group,Cordyceps Polysaccharide group(P < 0.05). Conclusion MSCs can be implanted in rat liver. Cordyceps polysaccharide combined with MSCs transplantation could decrease TIMP-1 expression,enhance MMP-13 expression,significantly promote collagen degradation,and reduce collagen deposition.
[中图分类号]
[基金项目]
广东省科技计划项目((2010B030700068)。