益气养阴方影响Lewis肺癌移植小鼠肿瘤生长的实验研究  

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

作　　者：杨国良[1] 胡丹丹[2] 

机构地区：[1]浙江省中西医结合医院肿瘤科,浙江杭州310009 [2]浙江中医药大学附属第三医院呼吸科,浙江杭州310005

出　　处：《中华全科医学》2016年第10期1623-1625,1788,共4页Chinese Journal of General Practice

基　　金：浙江省自然科学基金(LQ12H27006);浙江省中医药科技计划资助项目(2016ZA108);浙江省中医药科技计划项目(2015ZB084)

摘　　要：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。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 （1）Relative 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 ）. （2）The expression of Notch signal pathway and CD4^＋CD25^＋ Treg cell： the expression of Notchl 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 Jaggedl mRNA and Hesl mRNA in group B, C and D were lower than that in group A （ P 〈 0.05 ）

关 键 词：益气养阴方 NOTCH信号 肺肿瘤 CD4^+CD25^+TREG细胞 

分 类 号：R734.2[医药卫生—肿瘤] R730.23[医药卫生—临床医学]