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吗啡和低剂量氯胺酮对难治性癌痛患者T细胞的影响。

Effect of morphine and a low dose of ketamine on the T cells of patients with refractory cancer pain .

作者信息

Zhou Nai-Bao, Wang Kai-Guo, Fu Zhi-Jian

机构信息

Department of Anesthesiology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China.

Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.

出版信息

Oncol Lett. 2019 Oct;18(4):4230-4236. doi: 10.3892/ol.2019.10750. Epub 2019 Aug 16.

Abstract

The combination of morphine and ketamine is considered safe and efficacious in many patients. However, a considerable number of immunomodulatory effects have been reported to be produced by both morphine and ketamine. The aim of the present study was to assess the direct effect of morphine and a low dose of ketamine on the T cells of patients with refractory cancer pain . Venous blood was obtained from patients with refractory cancer pain and peripheral blood mononuclear cells were isolated using the Ficoll-Hypaque density gradient method. Anti-CD3 beads were used to isolate T cells by positive selection. Subsequently, the T cells were treated with vehicle, 200 ng/ml of morphine or 200 ng/ml of morphine + 100 ng/ml ketamine for 24 h, following which the cells were stimulated with anti-CD3 and anti-CD28. Flow cytometric analysis of CD3 T cells, and interleukin (IL)-2 and interferon (IFN)-γ in the supernatant, reverse transcription-quantitative PCR analysis for the detection of IL-2 and IFN-γ and western blotting for the detection of p65 nuclear factor (NF)-κB were performed. , the CD4 and CD8 T cell counts, CD4/CD8 ratio, secretion of IL-2 and IFN-γ in the supernatant, mRNA expression levels of IL-2 and IFN-γ and expression of p65 NF-κB were significantly decreased following treatment with morphine and morphine + ketamine, compared with results in the control group (all P<0.05). However, there was no significant difference between treatment with morphine and that with morphine + ketamine. Treatment with morphine + ketamine decreased the immune functions of patients with refractory cancer pain, although the effect of treatment with morphine and a low dose of ketamine did not differ significantly from that with morphine treatment alone.

摘要

吗啡和氯胺酮联合使用在许多患者中被认为是安全有效的。然而,据报道吗啡和氯胺酮都会产生相当多的免疫调节作用。本研究的目的是评估吗啡和低剂量氯胺酮对难治性癌痛患者T细胞的直接影响。从难治性癌痛患者中采集静脉血,采用Ficoll-泛影葡胺密度梯度法分离外周血单个核细胞。使用抗CD3磁珠通过阳性选择分离T细胞。随后,将T细胞用溶媒、200 ng/ml吗啡或200 ng/ml吗啡 + 100 ng/ml氯胺酮处理24小时,之后用抗CD3和抗CD28刺激细胞。对CD3 T细胞进行流式细胞术分析,检测上清液中的白细胞介素(IL)-2和干扰素(IFN)-γ,进行逆转录定量PCR分析以检测IL-2和IFN-γ,并进行蛋白质印迹法检测p65核因子(NF)-κB。结果显示,与对照组相比,吗啡和吗啡 + 氯胺酮处理后,CD4和CD8 T细胞计数、CD4/CD8比值、上清液中IL-2和IFN-γ的分泌、IL-2和IFN-γ的mRNA表达水平以及p65 NF-κB的表达均显著降低(所有P<0.05)。然而,吗啡处理与吗啡 + 氯胺酮处理之间没有显著差异。吗啡 + 氯胺酮处理降低了难治性癌痛患者的免疫功能,尽管吗啡和低剂量氯胺酮处理的效果与单独使用吗啡处理的效果没有显著差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5645/6732974/31a0a9985b8d/ol-18-04-4230-g00.jpg

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