益气养阴方影响Lewis肺癌移植小鼠肿瘤生长的实验研究

目的 通过对Lewis肺癌移植鼠肿瘤生长及肿瘤组织中Notch信号表达、CD4+CD25+ Treg细胞变化的观察，探讨益气养阴方干预肺癌的量效关系及机制。 方法 将肺癌移植小鼠随机分为4组，模型组只行造模；中药组按小鼠体重按不同剂量灌胃给药分为等效剂量组、大剂量组；化疗组以CTX腹腔注射化疗。记录各组小鼠瘤体大小，观察期满后留取标本行Notch信号表达检测。 结果 ①肿瘤相对体积(RTV)及肿瘤相对抑制率:大剂量组RTV低于其他3组(P＜0.01),化疗组RTV低于等效剂量组(P＜0.05)；大剂量组肿瘤抑制率较其他3组高(P＜0.05)。②肿瘤组织中Notch信号通路表达及CD4+CD25+ Treg细胞:等效剂量组Notch1 mRNA表达及CD4+CD25+ Treg细胞高于化疗组(P＜0.05);高剂量组较等效剂量组及化疗组低(P＜0.05);等效剂量组Notch3 mRNA表达与化疗组比较差异无统计学意义(P＞0.05);高剂量组较等效剂量组及化疗组Notch3 mRNA表达量降低(P＜0.05);等效剂量组、高剂量组、化疗组Jagged1 mRNA及Hesl mRNA表达均较模型组降低(P＜0.05),等效剂量组与化疗组Jagged1 mRNA及Hesl mRNA表达量降低(P＞0.05);高剂量组较等效剂量组及化疗组Jagged1 mRNA及Hesl mRNA表达量降低(P＜0.05)。 结论 益气养阴方剂有抑制Lewis肺癌移植小鼠肿瘤生长的作用，此种作用与益气养阴方剂的药物用量之间存在量效关系，且此种关系提示较大剂量的益气养阴方用量可能更有利于抑制Lewis肺癌细胞生长，而这种抑制作用与益气养阴方剂调控肿瘤组织中Notch1信号通路及CD4+CD25+ Treg细胞有关。 

Effect of Yiqi Yangyin Decoction on suppressing tumor growth in mice bearing Lewis lung cancer via the Notch signal pathway and CD4^+CD25^+ regulatory T cells

Objective To investigate the dose-effect relationship for Yiqi Yangyin Decoction on suppressing tumor growth via Notch signal pathway and CD4+CD25+ regulatory T cells in mice bearing Lewis lung cancer. Methods Sixty inbred C57BL/6 mouse bearing Lewis lung cancer were randomly divided into four groups:model group(Group A),chemotherapy group(Group B),equivalent dose group(Group C),high dose group(Group D).The mice in Group A were only developed an animal model.The mice in Group B were induced by intraperitoneal injection of CTX according 15 mg/kg every week.The mice in Group C were treated with Yiqi Yangyin decoction of 0.435 ml/kg by intragastric gavage,and the mice in Group D were treated with Yiqi Yangyin decoction of 1.36 ml/kg by intragastric gavage.The change of tumor volume was recorded.Then all the rats were sacrificed and all tumor tissues were weighted.The Notch signal expression in tumor tissues was tested. Results ①Relative tumor volume(RTV) and relative suppressing-tumor rate:RTV of every group(except model group) was reduced.RTV of Group D was reduced mostly among the four groups.RTV of Group B was reduced more than that of Group C(P<0.05);the relative suppressing-tumor rate of Group D was highest in all four groups(P<0.05).The rate of Group B was higher than that of Group C(P<0.05).②The expression of Notch signal pathway and CD4+CD25+ Treg cell:the expression of Notch1 mRNA and CD4+CD25+ Treg in group C was higher than that in group B(P<0.05),but the expression in group D was lower than those in the group B and C(P<0.05);there was no significant difference in the expression of Notch3 mRNA between group B and group C(P>0.05),but the expression of Notch3 mRNA in group D was lower than those in the group B and C(P<0.05);the expression of Jagged1 mRNA and Hesl mRNA in group B,C and D were lower than that in group A(P<0.05);there was no significant difference in the expression of Jagged1 mRNA and Hesl mRNA between group B and group C(P>0.05),but the expression of Jagged1 mRNA and Hesl mRNA in group D was lower than those in the group B and C(P<0.05). Conclusion Yiqi Yangyin decoction can suppress the Lewis lung cancer cell,and the effect has dose-response relationship.The mechanism maybe associated to the expression regulation of Notch1 signal pathway and CD4+CD25+ Treg.