“三两三”通过巨噬细胞发挥对吉非替尼所致皮疹的抗炎作用
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1.1)北京中医药大学,北京 100029;2.2)北京市鼓楼中医医院,北京 100009

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R3;R75

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Anti-inflammatory effects of “Sanliangsan” on gefitinibinduced skin rash via modulation of macrophages *
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1.1)Beijing University of Chinese Medicine, Beijing 100029, China;2.2)Beijing Gulou Hospital of traditional Chinese Medicine, Beijing 100009, China

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    摘要:

    吉非替尼所致的皮疹是治疗癌症中的难题,而中药验方三两三对于该皮疹具有较好的临床疗效。由于三两三治疗皮疹的机制尚不清楚,本文探究了该中药验方对吉非替尼所致皮疹的抗炎作用。将Brown Norway(BN)大鼠随机分为五组:野生型对照组、吉非替尼皮疹模型对照组、皮疹模型三两三低剂量组、中剂量组、高剂量组。采用吉非替尼(上午)和三两三(下午)同天给药4周。三两三低、中、高剂量组分别按照2 mg/kg/day、4 mg/kg/day、8 mg/kg/day 的剂量对BN模型大鼠进行灌胃,对照组给予纯净水。使用流式细胞仪对巨噬细胞进行分类;免疫组化检测蛋白质的表达;蛋白芯片检测与炎症相关的信号通路和炎症因子。结果表明,与野生型对照组相比,吉非替尼皮疹模型对照组中巨噬细胞炎症蛋白(MIP)-1、MIP-2、髓细胞触发受体-1 (TREM-1)和IL-17A的表达显著增加。三两三干预组与吉非替尼皮疹模型对照组相比,MIP-1、MIP-2、TREM-1和IL-17A的表达明显降低,且三两三对吉非替尼所致皮疹的抗炎作用与巨噬细胞的IL-17A信号通路密切相关。

    Abstract:

    Gefitinib induced rash is a common sequellae during cancer treatment. The mechanism and treatment of these rashes are unclear, therefore we investigated the anti-inflammatory effect of Sanliangsan on gefitinib induced rashes. Brown Norway (BN) rats were randomly selected and divided into five groups: control group, gefitinib rash model control group(model group), Sanliangsan model groups of low-dose, medium-dose, and high-dose(low,medium and high dose). Gifitinib was administered in the morning and Sanliangsan in the afternoon on the same day for 4 weeks .The BN model rats in the low-dose, medium-dose and high-dose groups were given 2 mg/kg/day, 4 mg/kg/day and 8 mg/kg/day of Sanliangsan respectively. The control group was given pure water. Macrophages were classified by flow cytometry. Protein expression was detected by immunohistochemistry. Protein chip array was used to detect the signaling pathways and inflammatory factors associated with inflammation. The results showed that the expressions of macrophage inflammatory protein (MIP)-1, MIP-2, myelocyte triggered receptor-1 (TREM-1) and IL-17A were significantly increased in the gefitinib rash model control group compared with the control group. The expressions of MIP-1, MIP-2, TREM-1 and IL-17A were significantly reduced in the Sanliangsan groups compared with the gefitinib rash model control group. It was also discovered that the anti-inflammatory effect of Sanliangsan on gefitinib-induced rash was closely related to the signaling pathway of IL-17A.

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万亮琴,宋晨晨,谭 琰,何 芳,张亚丽,王雅蕾,陈紫薇,张 策,谷若曦,张丁阳,王 旭,华 茜.“三两三”通过巨噬细胞发挥对吉非替尼所致皮疹的抗炎作用[J].生物化学与生物物理进展,2020,47(8):876-887

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历史
  • 收稿日期:2020-06-01
  • 最后修改日期:2020-06-01
  • 接受日期:2020-06-01
  • 在线发布日期: 2020-11-26
  • 出版日期: 2020-08-20