吗啡联合氯胺酮通过 JAK3/STAT5 通路改善宫颈癌痛并抑制免疫功能。

Morphine in Combination with Ketamine Improves Cervical Cancer Pain and Suppresses Immune Function via the JAK3/STAT5 Pathway.

机构信息

Department of Anesthesiology, Jianhu People's Hospital of Jiangsu Province, Yancheng City, Jiangsu Province, 224700, China.

Department of Gynecology, Jianhu People's Hospital of Jiangsu Province, Yancheng City, Jiangsu Province, 224700, China.

出版信息

Pain Res Manag. 2022 Apr 21;2022:9364365. doi: 10.1155/2022/9364365. eCollection 2022.

DOI:10.1155/2022/9364365

PMID:35492074

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9050326/

Abstract

BACKGROUND

The role of ketamine as an adjuvant for morphine in the treatment of cancer pain and immune functions has been confirmed. This study aimed to explore the role of morphine and ketamine on cancer pain and T cells of patients with cervical cancer (CC).

METHODS

T cells were isolated from peripheral blood mononuclear cells (PBMC) of CC patients by positive selection using anti-CD3 beads. The isolated T cells were assigned into three groups: the control group, the morphine group, and the morphine + ketamine (Mor + Ket) group. The percentages of CD4 and CD8 were analyzed by flow cytometry. The levels of interferon (IFN)-, interleukin (IL)-2, and IL-17 and the corresponding mRNA expression in vitro were determined using ELISA and qRT-PCR, respectively. Western blotting was used for detection of JAK3/STAT5 pathway-related proteins after naltrexone treatment in vitro. Afterwards, all the patients were further divided into the morphine group and the Mor + Ket group in accordance with the principles of the randomized and double-blind method to assess pain intensity.

RESULTS

Our in vivo results showed that drug combinations relieved cancer pain more effectively than morphine intervention. The in vitro results demonstrated that the combination of morphine and ketamine may decrease CD4 percentage, CD4/CD8 ratio, and the levels of IFN-, IL-2, and IL-17 via the JAK3/STAT5 pathway.

CONCLUSIONS

Our finding indicated that morphine-ketamine combination could improve cancer pain and repress immune function via the JAK3/STAT5 pathway in the progression of CC.

摘要

背景

氯胺酮作为吗啡治疗癌症疼痛和免疫功能的辅助药物的作用已得到证实。本研究旨在探讨吗啡和氯胺酮对宫颈癌（CC）患者癌痛和 T 细胞的作用。

方法

采用抗 CD3 磁珠阳性分选法从宫颈癌患者外周血单个核细胞（PBMC）中分离 T 细胞。将分离的 T 细胞分为三组：对照组、吗啡组和吗啡+氯胺酮（Mor+Ket）组。采用流式细胞术分析 CD4 和 CD8 的百分比。采用 ELISA 和 qRT-PCR 分别测定体外干扰素（IFN）-、白细胞介素（IL）-2 和 IL-17 的水平及其相应的 mRNA 表达。体外用纳曲酮处理后，采用 Western blot 检测 JAK3/STAT5 通路相关蛋白。之后，所有患者均根据随机双盲原则进一步分为吗啡组和 Mor+Ket 组，以评估疼痛强度。