抑制AFP表达对肝癌模型小鼠肝脏损伤修复的影响及相关机制

Effect of inhibiting the expression of AFP on the repair of liver injury in liver cancer model mice and related mechanisms

目的探讨抑制甲胎蛋白(AFP)表达对肝癌模型小鼠肝脏损伤修复的影响及相关机制。方法注射Walker-256癌肉瘤细胞株细胞悬液0.1 mL(约2×10^7个细胞)至小鼠肝脏组织建立移植性肝癌模型。将45只肝癌模型小鼠按随机数字表法分为3组-模型组、对照组与AFP组。AFP组与对照组采用EntransterTM-in vivo体内转染shRNA-AFP与shRNA-NC,模型组以等剂量的磷酸盐缓冲液进行转染,7 d 1次,共转染4次。观察与记录小鼠体重、血液学指标与肝脏p53表达水平变化情况。结果AFP组治疗第14天与治疗第28天的体重高于模型组与对照组,瘤体直径、血清AFP含量、CD8^+T细胞比率低于模型组与对照组,差异有统计学意义(P<0.05),模型组与对照组比较差异无统计学意义(P>0.05)。AFP组治疗第28天的肝脏组织中p53蛋白相对水平均低于模型组与对照组,差异有统计学意义(P<0.05),模型组与对照组比较,差异无统计学意义(P>0.05)。结论抑制AFP表达能促进肝癌模型小鼠肝脏损伤修复,增加小鼠体重,抑制肝脏组织p53的表达与肿瘤生长,改善小鼠的免疫状态。

Objective To investigate the effect of inhibiting the expression of Alpha-fetoprotein(AFP)on the repair of liver injury in liver cancer model mice and related mechanisms.Methods The transplanted liver cancer model was established by injecting 0.1 mL of Walker-256 carcinosarcoma cell line suspension(about 2×10^7 cells)into mice liver tissue.Forty-five cases of liver cancer model mice were divided into three groups-model group,control group and AFP group according to the random number table method.The AFP group and the control group were transfected with shRNA-AFP and shRNA-NC in vivo used EntransterTM-in vivo,and the model group were transfected with the same dose of phosphate buffer,once every 7 days for total of 4 transfections.Observed and recorded the changes of mice body weight,hematological indicators and liver p53 expression levels.Results The body weight of the AFP group on the 14th and 28th day after treatment were higher than that of the model group and the control group,and the tumor diameter,serum AFP content,and the proportion of CD8^+T cells were lower than the model group and the control group,the difference was statistically significant(P<0.05),there were no statistically significant difference compared between the model group and the control group(P<0.05).The relative levels of p53 protein in liver tissue of the AFP group were lower than the model group and the control group on the 28th day of treatment,the difference was statistically significant(P<0.05),and there were no significant difference compared between the model group and the control group(P<0.05).Conclusion Inhibiting the expression of AFP can promote the repair of liver injury in liver cancer model mice,increase the weight of mice,inhibit the expression of p53 in liver tissues and tumor growth,and improve the immune status of mice.