CAJ | 학술논문

目的观察骨髓间充质干细胞(BMSCs)移植干预肝纤维化是否以转化生长因子-B1(TGF-β1)为作用靶点,并观察BMSCs对肝癌生长的影响.方法建立四氯化碳诱导的大鼠肝纤维化模型(n=16)和二乙基亚硝胺诱发性大鼠肝癌模型(n=16),分析TGF-β1在BMSCs移植减轻纤维化中的作用以及对肝癌发生的影响.结果在大鼠肝纤维化模型中,模型组与干预组肝脏炎症活动度Scheuer评分均值为3.58和0.42(u=-4.22,P＜0.01),纤维化程度Schmid M评分为5.17和1.58分(u=-3.65,P＜0.01),α-平滑肌肌动蛋白(α-SMA)评分为2.25和0.58分(u=-2.93,P ＜0.01),TGF-β1含量在两组间差异有统计学意义(F=11.024,P＜0.05).在大鼠肝癌模型中,BMSCs移植可以抑制细胞周期(G1期:P＜0.01,G2期:P＜0.01,S期:P＜0.01),但不能减少肝癌发生(P＞0.05),TGF-β1的含量在两组间差异无统计学意义(P＞0.05).结论 BMSCs移植可能通过抑制TGF-β1的分泌、减少肝星状细胞激活而减缓肝纤维化;BMSCs移植可以抑制细胞周期,其作用并非通过TGF-β1途径.
목적 관찰골수간충질간세포(BMSCs)이식간예간섬유화시부이전화생장인자-B1(TGF-β1)위작용파점,병관찰BMSCs대간암생장적영향.방법 건립사록화탄유도적대서간섬유화모형(n=16)화이을기아초알유발성대서간암모형(n=16),분석TGF-β1재BMSCs이식감경섬유화중적작용이급대간암발생적영향.결과 재대서간섬유화모형중,모형조여간예조간장염증활동도Scheuer평분균치위3.58화0.42(u=-4.22,P＜0.01),섬유화정도Schmid M평분위5.17화1.58분(u=-3.65,P＜0.01),α-평활기기동단백(α-SMA)평분위2.25화0.58분(u=-2.93,P ＜0.01),TGF-β1함량재량조간차이유통계학의의(F=11.024,P＜0.05).재대서간암모형중,BMSCs이식가이억제세포주기(G1기:P＜0.01,G2기:P＜0.01,S기:P＜0.01),단불능감소간암발생(P＞0.05),TGF-β1적함량재량조간차이무통계학의의(P＞0.05).결론 BMSCs이식가능통과억제TGF-β1적분비、감소간성상세포격활이감완간섬유화;BMSCs이식가이억제세포주기,기작용병비통과TGF-β1도경.
Objective To investigate the effects of bone mesenehymal stem cells (BMSCs) transplantation on rat hepatic fibrogenesis/hepatoma via transforming growth factor-β1 (TGF-β1).Methods The hepatic fibrosis model and hepatoma model were induced by carbon tetrachloride (CCl4) and diethylnitrosamine respectively in rats (n =16 each).The BMSCs of the forth generation were respectively injected into the rats via the caudalis vena.Effects of TGF-β1 on the BMSCs transplantation on hepatic fibrogenesis and hepatoma in rats were investigated.Results In the hepatic fibrosis model,the mean value of Scheuer inflammation score,Schmid M fibrosis score and the activation score of HSC showed significant difference between control group and intervention group,with 3.58 and 0.42 (u =-4.22,P ＜ 0.01),5.17 and 1.58 (u =-3.65,P ＜0.01),2.25 and 0.58 (u =-2.93,P ＜0.01),respectively.There was also significant difference in the contents of TGF-β1 between two groups (F =11.024,P ＜ 0.05).In the hepatoma model,the cell cycle was restrained in intervention group and most cells were arrested in G1 phase,and in control group,most cells were arrested in S phase (G1 phase P ＜ 0.01,G2 phase P ＜ 0.01,S phase P ＜0.01).However,there was no significant difference in the incidence of liver cancer between two groups (P ＞ 0.05).Further more,the mean value of TGF-β1 showed no significant difference between two groups (P ＞ 0.05).Conclusion BMSCs transplantations can reduce hepatic stellate cells activation and thus slow down the process of liver fibrosis probably by inhibiting the secretion of TGF-β1.BMSCs can inhibit the cell cycle not through the TGF-β1 pathway.