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地佐辛促进手术小鼠模型中 T 淋巴细胞的激活和抑制肿瘤转移。

Dezocine promotes T lymphocyte activation and inhibits tumor metastasis after surgery in a mouse model.

机构信息

Department of Anesthesiology, People's Hospital of Caoxian, Fumin Street, Caoxian, Heze, 274400, Shandong, China.

Department of Anesthesiology, People's Hospital of Liaocheng, No. 67 Dongchang West Street, Liaocheng, 252000, Shandong, China.

出版信息

Invest New Drugs. 2020 Oct;38(5):1342-1349. doi: 10.1007/s10637-020-00921-6. Epub 2020 Mar 13.

Abstract

Dezocine is an opioid analgesic with both μ-receptor agonist and antagonist activities. Administration of opioids influences the immune system through immune cells. Dendritic cells (DC) play crucial functions in inducing T cell response and mediating immune functions. DC surface displays several different opioid receptors whose expression is induced during DC maturation. We aimed to explore the effects of dezocine on DCs and T cells, as well as on tumor treatment. Mice were intraperitoneally administrated with increasing doses of dezocine (0.75, 1.25 and 2.0 mg/kg). Mouse bone marrow-derived dendritic cells (BMDCs) were then isolated from the bone marrow. The BMDC surface markers were evaluated by flow cytometry. T cell proliferation was assessed by the carboxyfluorescein succinimidyl ester assay. The number of mature DCs were increased by dezocine treatment in both human umbilical cord blood and mouse peripheral blood, suggesting that dezocine enhanced BMDC maturation. Dezocine-treated BMDCs promoted CD8+ T cell proliferation and cytotoxicity, while dezocine treatment inhibited tumor metastasis in mice. We therefore conclude that the administration of dezocine promotes BMDC maturation and inhibits tumor metastasis through elevating CD8+ T cell proliferation and cytotoxicity.

摘要

地佐辛是一种具有μ受体激动剂和拮抗剂活性的阿片类镇痛药。阿片类药物的给药会通过免疫细胞影响免疫系统。树突状细胞 (DC) 在诱导 T 细胞反应和调节免疫功能方面发挥着至关重要的作用。DC 表面显示出几种不同的阿片受体,其表达在 DC 成熟过程中被诱导。我们旨在探讨地佐辛对 DC 和 T 细胞以及肿瘤治疗的影响。将小鼠腹腔内给予递增剂量的地佐辛(0.75、1.25 和 2.0mg/kg)。然后从骨髓中分离出小鼠骨髓来源的树突状细胞(BMDC)。通过流式细胞术评估 BMDC 表面标志物。通过羧基荧光素琥珀酰亚胺酯测定法评估 T 细胞增殖。地佐辛处理增加了人脐血和小鼠外周血中成熟 DC 的数量,这表明地佐辛增强了 BMDC 的成熟。地佐辛处理的 BMDC 促进了 CD8+T 细胞的增殖和细胞毒性,而地佐辛处理抑制了小鼠的肿瘤转移。因此,我们得出结论,地佐辛通过提高 CD8+T 细胞的增殖和细胞毒性来促进 BMDC 的成熟并抑制肿瘤转移。

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