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不同浓度羟考酮反复腹腔注射对小鼠免疫功能的影响。

Effect of repeated intraperitoneal injections of different concentrations of oxycodone on immune function in mice.

作者信息

Chen Sumeng, Liu Jingjing, Huang Shaoqiang

机构信息

Department of Anesthesia, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.

出版信息

Front Pharmacol. 2024 Jun 17;15:1370663. doi: 10.3389/fphar.2024.1370663. eCollection 2024.

Abstract

BACKGROUND

The effect of oxycodone as an opioid receptor agonist on immune function is still controversial. In this study, we investigated the possible effects of oxycodone on immune function in mice and its possible mechanisms of action.

METHODS

By repeated intraperitoneal injections of 25 mg/kg morphine and 5 mg/kg, 20 mg/kg, and 60 mg/kg oxycodone, we assessed possible changes in the number of splenic lymphocytes and inflammatory cytokines in the serum of mice. CD4 T cells and CD8 T cells were sorted from the spleen to observe whether the expression levels of opioid receptors and downstream signals were altered.

RESULTS

Repeated administration of oxycodone at a dose above 20 mg/kg resulted in significant weight loss. Repeated administration of oxycodone exhibits significant dose-dependent reduction in CD4 T cells, with little effect on CD8 T cells and little effect on inflammatory cytokine levels. Low- and intermediate-dose oxycodone increased the mRNA expression level of MOR, KOR, and DOR to varying degrees. Moreover, oxycodone increases the mRNA expression levels of the TLR4 signaling pathway to varying degrees.

CONCLUSION

Repeated intraperitoneal injection of oxycodone induces immunosuppression in mice.

摘要

背景

羟考酮作为阿片受体激动剂对免疫功能的影响仍存在争议。在本研究中,我们调查了羟考酮对小鼠免疫功能的可能影响及其可能的作用机制。

方法

通过反复腹腔注射25mg/kg吗啡以及5mg/kg、20mg/kg和60mg/kg羟考酮,我们评估了小鼠脾脏淋巴细胞数量和血清中炎性细胞因子的可能变化。从脾脏中分离出CD4 T细胞和CD8 T细胞,观察阿片受体及其下游信号的表达水平是否改变。

结果

反复给予剂量高于20mg/kg的羟考酮导致体重显著减轻。反复给予羟考酮可使CD4 T细胞显著减少,且呈剂量依赖性,对CD8 T细胞影响较小,对炎性细胞因子水平影响不大。低剂量和中剂量羟考酮可不同程度地提高MOR、KOR和DOR的mRNA表达水平。此外,羟考酮可不同程度地提高TLR4信号通路的mRNA表达水平。

结论

反复腹腔注射羟考酮可诱导小鼠免疫抑制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99f9/11215192/b4f30769f2fa/fphar-15-1370663-g001.jpg

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