双黄升白颗粒对小鼠化疗骨髓抑制期骨髓EGFR信号通路的调控作用  

Regulatory effect of “Shuanghuang Shengbai Granules”on EGFR signal pathway in inhibition period in mice after chemotherapy

作　　者：王鹤潼[1] 王立芳[1] 徐振晔[1] 王爽[1] 康小红[1] 司海龙[1] 阮明玉 

机构地区：[1]上海中医药大学附属龙华医院肿瘤科,上海中医药大学中医肿瘤研究所,上海200032

出　　处：《上海中医药杂志》2014年第10期93-98,共6页Shanghai Journal of Traditional Chinese Medicine

基　　金：上海市科委自然基金资助项目(12ZR1431800);上海中医药大学附属龙华医院课题资助项目(LYTD-18);上海市卫生局基金资助项目(2011XY006)

摘　　要：目的观察双黄升白颗粒对化疗后骨髓抑制小鼠骨髓组织EGFR信号通路主要成员表皮生长因子(EGF)、表皮生长因子受体(EGFR)、K-ras蛋白及基因表达的影响,并探讨其作用机制。方法 Balb/C裸鼠80只,随机分为10组,即空白组(6 d、8 d)、模型组(6 d、8 d)、厄洛替尼组(6 d、8 d)、厄+双组(6 d、8 d)、双黄组(6 d、8 d)。除空白组外,其余各组以腹腔注射环磷酰胺(CTX)建立化疗骨髓抑制模型。观察各组小鼠给药6 d、8 d的外周血白细胞计数,以酶联免疫吸附试验(ELISA)检测血清EGF表达,以蛋白质印迹法(Western Blot)检测骨髓组织中EGFR信号通路主要成员EGF、EGFR、K-ras的变化,以实时荧光定量PCR(RTFQ PCR)检测骨髓组织中EGF mRNA、EGFR mRNA、K-ras mRNA的表达。结果给药第8 d时,除空白组外,其余各组小鼠外周血白细胞均有一定回升(P<0.01),双黄组化疗骨髓抑制小鼠外周血白细胞数量明显高于除空白组外的其余各组(P<0.01);除厄洛替尼组血清EGF表达稍高外(P<0.05,P<0.01),其余各组别间血清EGF表达差异不显著(P>0.05);双黄组小鼠骨髓组织EGF、EGFR及K-ras蛋白及其mRNA表达明显高于模型组、厄洛替尼组及厄+双组(P<0.01),而厄+双组表达明显低于双黄组,高于厄洛替尼组(P<0.01)。给药6 d和给药8 d比较,各指标差异均无统计学意义(P>0.05)。结论双黄升白颗粒可明显缓解小鼠化疗后骨髓抑制,其作用机制与EGFR信号通路有相关性。Objective To observe the effect of ＂Shuanghuang Shengbai Granules＂ on EGF, EGFR K-ras protein and protein expression in bone marrow of mice after chemotherapy and to explore its mechanism. Methods Eighty mice were randomized into ten groups： blank group （ 6, 8 d）, model＂ group （ 6, $ d ）, Erlotinib group （6, 8 d）, Erlotinib ＋ ＂Shuanghuang Shengbai Granules＂ （6, 8 d） group, ＂Shuanghuang Shengbai Granules＂ group （6, 8 d）. Except for the blank group, models in the other groups were injected by cyclophosphamide. WBC was observed after administration for 6 and 8 days. The EGF expression was detected by ELISA. The changes of EGF, EGFR and K-ras were detected by Western Blot method. Expressions of EGF mRNA, EGFR mRNA and K-ras mRNA were detected by realtime fluorescence quantitative PCR method in bone marrow. Results Except for the blank group, WBC was increased in the other groups at the 8th day （ P 〈 0.01 ）, and WBC in the ＂Shuanghuang Shengbai Granules＂ group was higher than that of the other groups （ P 〈 0.01 ） ; the EGF expression was more obvious in the Erlotinib group （ P 〈 0.05, P 〈 0.01 ）, no significant diference was found in the serum EGF expression in other groups （ P 〉 0. 05 ） ; the expressions of EGF, EGFR and K-protein and EGF mRNA, EGFR mRNA and K-protein in the ＂Shuanghuang Shengbai Granules＂ group were higher than that of the model group, Erlotinib group and Erlotinib ＋ ＂Shuanghuang shengbai Granules＂ （ P 〈 0. 01 ）, and the expression in the Erlotinib ＋ ＂Shuanghuang Shengbai Granules＂ group was lower than that of the ＂Shuanghuang Shengbai Granules＂ group, but was higher than that of the Erlotinib group （ P 〈 0. 01 ）. No significant difference was found in all indicators between the 6 d administration and 8 d administration （ P 〉 0.05 ）. Conclusion ＂Shuanghuang Shengbai Granules＂ can obviously relieve the myelosuppression after chemotherapy in mice, and its mechanism has certain correlation with

关 键 词：双黄升白颗粒 化疗骨髓抑制 表皮生长因子 表皮生长因子受体 K-ras蛋白 

分 类 号：R285.5[医药卫生—中药学]