十全大补汤对SV40T抗原转基因小鼠晶状体自发肿瘤的抑制作用及其分子机制

摘要

目的:探讨十全大补汤对SV40 T抗原转基因(TG)小鼠晶状体自发肿瘤的抑制作用,阐明其抑癌的分子机制.方法:SV40 T抗原TG小鼠随机分为对照组(n=39)和药物处理组(n=25),对照组小鼠正常喂食,药物处理组小鼠出生3周后开始喂食添加十全大补汤的饲料,记录每只小鼠生存时间.在喂食十全大补汤8周和15周时,随机抽取各组小鼠(n=3)尾静脉血,检测血清氨基酸水平.取血后小鼠麻醉致死并取出肝脏,利用基因芯片杂交检测小鼠肝脏组织中与核糖体功能相关的基因表达差异.结果:生存分析,与对照组比较,药物处理组TG小鼠生存率明显升高(P＜0.05).氨基酸检测,与对照组比较,喂食十全大补汤8周时,药物处理组TG小鼠血清中丙氨酸、缬氨酸、亮氨酸、异亮氨酸、苏氨酸、甲硫氨酸、脯氨酸、酪氨酸、赖氨酸、肌氨酸、瓜氨酸、鸟氨酸和羟赖氨酸水平升高(P＜0.05),胱硫醚、牛磺酸、甲基组氨酸、肌肽和乙醇胺水平降低(P＜0.05);15周时,与对照组比较,药物处理组TG小鼠血清中苏氨酸和瓜氨酸水平升高(P＜0.05),其他氨基酸水平无明显变化(P＞0.05).基因芯片杂交检测,与对照组比较,药物处理组TG小鼠肝组织表达的9 083个基因中与核糖体功能相关的13个基因发生改变(P＜0.05).结论:十全大补汤能改善TG小鼠血清氨基酸水平,增强肝脏核糖体蛋白合成,通过改善肝脏功能明显延长TG小鼠生存期.%Objective:To explore the inhibitory effect of Shiquandabu decoction on the spontaneous len tumor of the SV40 T antigen transgenic (TG) mice,and to clarify its molecular mechanism.Methods:The SV40 T antigen TG mice were randomly divided into control group (n=39) and drug treatment group (n=25).The mice in control group were fed normally,while the mice in drug treatment group were fed with Shiquandabu decoction at the 3rd week after birth,the survival time of mice was recorded.Three mice in control group and drug treatment group were randomly chosen to collect the blood from the tail vein and the amino acid levels were measured respectively 8 and 15 weeks after Shiquandabu decoction administration.Then the mice were sacrificed and the liver tissue wascollected.Gene chip hybridization was used to detect the differences in the expressions of ribosomal function related genes in liver tissue of the mice in two groups and the related signal pathway was explored.Results:The survival analysis demonstrated that the survival rate of TG mice in drug treatment was higher than that in control group (P＜0.05).Compared with control group,the serum levels of alanine,valine,leucine,isoleucine,threonine,methionine,proline,tyrosine,lysine,sarcosine,citrulline,ornithine and hydroxylysine of the mice in drug treatment group 8 weeks after administration of Shiquandabu decoction were increased (P＜0.05);and the serum levels of cystathionine,taurine,methylhistidine,anserine and ethanolamine were decreased (P＜0.05).Fifteen weeks after administration,compare with control group,the serum levels of threonine and citrulline of the mice in drug teeatment group were increased (P＜0.05),but the serum levels of other amino acids had no significant difference (P＞ 0.05).The canonical analysis showed that thirteen genes involved in ribosomal function from 9 083 genes in liver tissue in drug treatment group had the changes compared with control group (P＜ 0.05).Conclusion:Shiquandabu decoction can effectively prolong the lifetime of the TG mice by improving the levels of serum amino acids and promoting the liver ribosomal protein synthesis.