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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.

DOI:10.1007/s10637-020-00921-6
PMID:32170576
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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本文引用的文献

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The application of dexmedetomidine combined with dezocine in thoracoscopic radical resection of lung cancer and its effect on awakening quality of patients.右美托咪定联合地佐辛在肺癌胸腔镜根治术中的应用及对患者苏醒质量的影响。
Eur Rev Med Pharmacol Sci. 2019 Sep;23(17):7694-7702. doi: 10.26355/eurrev_201909_18893.
2
Effects of dezocine for the prevention of postoperative catheter-related bladder discomfort: a prospective randomized trial.地佐辛预防术后导尿管相关膀胱不适的效果:一项前瞻性随机试验
Drug Des Devel Ther. 2019 Apr 23;13:1281-1288. doi: 10.2147/DDDT.S199897. eCollection 2019.
3
Effects of dezocine and sufentanyl for postoperative analgesia on activity of NK, CD4 and CD8 cells in patients with breast cancer.
地佐辛通过内质网应激途径诱导人宫颈癌Hela细胞凋亡。
Toxicol Res (Camb). 2022 May 30;11(3):498-510. doi: 10.1093/toxres/tfac026. eCollection 2022 Jun.
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Dezocine Has the Potential to Regulate the Clinical and Biological Features of Tumors.地佐辛有可能调节肿瘤的临床和生物学特征。
Drug Des Devel Ther. 2022 Apr 20;16:1121-1129. doi: 10.2147/DDDT.S356863. eCollection 2022.
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Effects of Dezocine and Sufentanil on Th1/Th2 Balance in Breast Cancer Patients Undergoing Surgery.地佐辛和舒芬太尼对行手术治疗的乳腺癌患者 Th1/Th2 平衡的影响。
Drug Des Devel Ther. 2021 Dec 2;15:4925-4938. doi: 10.2147/DDDT.S326891. eCollection 2021.
6
Effect of Dezocine on the Ratio of Th1/Th2 Cytokines in Patients Receiving Postoperative Analgesia Following Laparoscopic Radical Gastrectomy: A Prospective Randomised Study.地佐辛对腹腔镜根治性胃切除术后患者接受术后镇痛时 Th1/Th2 细胞因子比值的影响:一项前瞻性随机研究。
Drug Des Devel Ther. 2021 May 27;15:2289-2297. doi: 10.2147/DDDT.S306120. eCollection 2021.
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Effects of dezocine on prevention of propofol injection pain: a meta-analysis.地佐辛预防丙泊酚注射痛的效果:一项荟萃分析。
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