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益神颗粒联合5-氟尿嘧啶抑制肿瘤生长的作用机制研究 被引量:1

The mechanism of inhibitory effect of Yishen granule combined with 5-fluorouracil on tumor growth
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摘要 目的通过益神颗粒联合5-氟尿嘧啶(5-fluorouracil,5-FU)对Colon26结肠癌荷瘤小鼠肿瘤生长抑制试验,探讨益神颗粒的免疫调节作用机制。方法将40只BALB/c小鼠建立Colon26结肠癌荷瘤小鼠模型,随机分为模型组、5-FU组(20 mg/kg)、益神颗粒组(2.5 g/kg)和5-FU(20 mg/kg)+益神颗粒(2.5 g/kg)联合用药组,每组10只。给药12 d后,检测抑瘤率、胸腺和脾脏指数、脾淋巴细胞增殖能力、自然杀伤(natural killer,NK)细胞杀伤活性及腹腔巨噬细胞吞噬功能,采用多因子流式检测技术检测干扰素-(interferon-,IFN-)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白介素-2(interleukin-2,IL-2)水平,流式细胞仪检测脾脏淋巴细胞亚群。结果给药12 d后,与模型组比较,5-FU组、益神颗粒组和联合用药组抑瘤率分别为52.6%、32.0%和65.3%;与模型组比较,益神颗粒组小鼠脾淋巴细胞增殖能力、NK细胞杀伤活性、腹腔巨噬细胞吞噬功能均增强(P<0.01),IL-2水平增加(P<0.01),CD4/CD8细胞比值增大(P<0.05);与5-FU组比较,联合用药组胸腺指数和脾脏指数增大(P<0.01),脾淋巴细胞增殖能力、NK细胞杀伤活性、巨噬细胞吞噬功能增强(P<0.05),TNF-α和IL-2水平增加(P<0.05),CD4/CD8细胞比值增大(P<0.05)。结论益神颗粒具有显著的增强免疫功能作用,与化疗药5-FU联合使用比单独用5-FU具有更强的抑制肿瘤作用,其机制主要与改善、增强因使用化疗药导致的免疫功能降低相关。 Objective To investigate the immunomodulatory mechanism of Yishen granule combined with 5-fluorouracil(5-FU)on tumor growth inhibition in Colon26 colon tumor bearing mice.Methods Total 40 BALB/c mice were used to establish Colon26 colon tumor bearing mouse model,and then the mice were randomly divided into model group,5-FU group(20 mg/kg),Yishen granule group(2.5 g/kg)and 5-FU+Yishen granule combination group(20 mg/kg+2.5 g/kg),with 10 mice in each group.After 12 days of administration,the tumor inhibition rate,thymus and spleen index,splenic lymphocyte proliferation,natural killer(NK)cell killing activity and peritoneal macrophage phagocytic were detected.The levels of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α)and interleukin-2(IL-2)were measured by multifactor flow cytometry.Splenic lymphocyte subsets were detected by flow cytometry.Results After 12 days of administration,compared with the model group,the tumor inhibition rates of 5-FU group,Yishen granule group and combination group were 52.6%,32.0%and 65.3%,respectively.Compared with the model group,the spleen lymphocyte proliferation,NK cell killing activity and peritoneal macrophage phagocytosis in Yishen granule group were enhanced(P<0.01),the level of IL-2 was increased(P<0.01),the ratio of CD4/CD8cells was increased(P<0.05).Compared with 5-FU group,the thymus index and spleen index in combination group were increased(P<0.01).The splenic lymphocyte proliferation,NK cell killing activity and macrophage phagocytosis were enhanced in combination group(P<0.05),the levels of TNF-αand IL-2 increased(P<0.05),the ratio of CD4/CD8cells increased(P<0.05).Conclusion Yishen granule has a significant effect on enhancing immune function,and the combination with chenmotherapy drug 5-FU has a stronger tumor inhibition effect than chenmotherapy drug 5-FU alone,and its mechanism is mainly related to improving and enhancing the immune function reduction caused by the use of chenmotherapy drugs.
作者 雷博 张艳艳 潘绵立 沈龙海 王松坡 LEI Bo;ZHANG Yanyan;PAN Mianli;SHEN Longhai;WANG Songpo(State Key Laborary of New Drug and Pharmaceutical Process,China State Institute of Pharmaceutical Industry,Shanghai 200437,China;Shanghai Professional Technical Service Center for Biological Material Druggability Evaluation,Shanghai 200437,China;Department of Traditional Chinese Medicine,Shanghai General Hospital,Shanghai Jiao Tong University,Shanghai 200080,China)
出处 《世界临床药物》 2022年第4期386-393,共8页 World Clinical Drug
基金 上海市科技发展基金(17401901200、19401970100) 上海市进一步加快中药事业发展三年行动计划,“海派中医”张氏内科流派诊疗中心[ZY(2018-2020)-CCCX-1002]。
关键词 益神颗粒 5-氟尿嘧啶 结肠癌 Colon26细胞 免疫调节 Yishen granule 5-fluorouracil colon cancer Colon26 cell immune regulation
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