移植骨髓间充质干细胞肝癌大鼠细胞凋亡及炎症因子的动态变化

Effect of rat bone marrow mesenchymal stem cells on dynamic changes of inflammatory factors and apoptosis index during hepatocarcinogenesis

背景:骨髓间充质干细胞移植后对肝癌细胞凋亡及炎症因子的影响,尚没有详细的报道。目的:观察骨髓间充质干细胞移植后大鼠血清炎症因子水平及肝癌细胞凋亡情况。方法:选取60只健康SD大鼠随机分为正常组、对照组及移植组,每组20只。对照组及移植组大鼠喂食普通饲料和二乙基亚硝胺溶液,以诱导大鼠肝癌模型,造模后移植组经尾静脉注射骨髓间充质干细胞。移植2周后,采用ELISA检测血清CXCL5、白细胞介素8、白细胞介素6水平,RT-PCR检测肝组织HNF1αmR NA表达,免疫组化法检测肝组织Bcl-2、Bax表达,TUNEL技术检测肝癌细胞凋亡指数。结果与结论:(1)对照组血清CXCL5、白细胞介素8、白细胞介素6水平明显高于正常组(P<0.05),移植组CXCL5、白细胞介素8、白细胞介素6水平较对照组明显下降(P<0.05),与正常组接近(P>0.05);(2)对照组肝组织HNF1α表达显著低于正常组(P<0.05),移植组HNF1α表达又明显上调,与对照组比较,差异有显著性意义(P<0.05);(3)移植组肝组织Bcl-2表达较对照组明显下调,而Bax表达较对照组明显上调(P<0.05);(4)与对照组比较,移植组肝癌细胞凋亡指数明显上升(P<0.05);(5)结果表明,骨髓间充质干细胞移植有助于减少肝癌大鼠血清炎症水平、促进肝癌细胞凋亡,有利于肝细胞分化及再生。

BACKGROUND： Bone marrow mesenchymal stem cell transplantation has not been thoroughly reported on its effects on apoptosis in hepatoma carcinoma cells and inflammatory factor level. OBJECTIVE： To investigate the effect of rat bone marrow mesenchymal stem cells on dynamic change of inflammatory factors and cell apoptosis during hepatocarcinogenesis. METHODS： Sixty healthy Sprague-Dawley rats were divided randomly into healthy group（n=30）, control group（n=30） and transplantation group（n=30）. Healthy group was given ordinary feed and normal water, while other groups were given diethylnitrosamine solution in drinking water to induce liver cancer models. Then, rats in the transplantation group were subjected to bone marrow mesenchymal stem cell transplantation via the tail vein. Two weeks after cell transplantation, CXCL5, interleukin-8 and interleukin-6 levels were tested by ELISA, m RNA level of hepatocyte nuclear factor 1α detected by RT-PCR, expression of Bcl-2 and Bax in liver tissue measured by immunohistochemical method, and liver cancer cell apoptosis index detected by TUNEL technique. RESULTS AND CONCLUSION： After modeling, the expressions of CXCL5, interleukin-8 and interleukin-6 in the control group were significantly higher than those in the healthy group（P〈 0.05）, while these indexes were reduced significantly after bone marrow mesenchymal stem cell transplantation（P 〈0.05） and close to the normal levels（P 〉0.05）. Bone marrow mesenchymal stem cell transplantation significantly up-regulated the mR NA level of hepatocyte nuclear factor 1α in the liver tissue that was decreased obviously after modeling（P〈 0.05）. In addition, the expression of Bcl-2 was reduced, while the expression of Bax and the apoptosis index increased significantly in the transplantation group compared with the control group（P〈 0.05）. These findings indicate that bone marrow mesenchymal stem cell transplantation contributes to hepatocyte differentiation and regeneration in liver cancer rats by reducing serum inflammatory factor levels and promoting apoptosis in hepatoma carcinoma cells.