研究阿片类药物对炎症期间小胶质细胞亚硝酸盐和一氧化氮合酶(iNOS)产生及吞噬作用的影响。
Investigation of the Effects of Opioids on Microglial Nitrite and Nitric Oxide Synthase (iNOS) Production and Phagocytosis during Inflammation.
机构信息
Department of Anesthesiology and Perioperative Medicine, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450000, China.
出版信息
Comb Chem High Throughput Screen. 2023;26(10):1900-1906. doi: 10.2174/1386207326666221111093915.
AIM
This study aimed to investigate how opioids affect phagocytosis and microglial nitrite and nitric oxide synthase (iNOS) production during inflammation.
BACKGROUND
Opioids are a group of chemicals that are naturally found in the opium poppy plant and exert a variety of effects on the brain, including pain alleviation in some cases. They are commonly used in surgery and perioperative analgesia. However, research on the impact of opioids on microglial inflammatory factor production and phagocytosis is limited.
OBJECTIVES
This study was designed to investigate the effects of opioids on inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) generation. Moreover, the influence of opioids on the engulfment of C8-B4 microglial cells after stimulation with LPS was also examined.
METHODS
C8-B4 mouse microglial cells were exposed to various concentrations of opioids after stimulation with lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Nitrite production was assayed. The iNOS and Cox-2 were determined by Western blotting, and fluorescent immunostaining was performed to assess the percentage of microglia that engulfed fluorescent microspheres in total microglia cultivating with opioids after being activated by LPS.
RESULTS
After LPS and IFN-γ stimulation, microglia produced lower amounts of nitric oxide (NO) production with buprenorphine, salvinorin A, and naloxone (P<0.05). When combined with naloxone, no significant differences were found than buprenorphine. It was observed that buprenorphine and salvinorin A could suppress iNOS expression activated by LPS and IFN-γ. Phagocytosis was greatly increased after LPS stimulation, and a significant increase was observed after adding salvinorin A.
CONCLUSION
Buprenorphine and salvinorin A were found to reduce NO production and iNOS induction in microglial cells activated by LPS and IFN-γ. Salvinorin A promoted the phagocytosis of microglia cells treated by LPS.
目的
本研究旨在探讨阿片类药物在炎症过程中如何影响吞噬作用以及小胶质细胞亚硝酸盐和一氧化氮合酶（iNOS）的产生。
背景
阿片类药物是一组天然存在于罂粟植物中的化学物质，对大脑有多种作用，包括在某些情况下缓解疼痛。它们通常在手术中和围手术期镇痛中使用。然而，关于阿片类药物对小胶质细胞炎症因子产生和吞噬作用的影响的研究有限。
目的
本研究旨在探讨阿片类药物对诱导型一氧化氮合酶（iNOS）活性和一氧化氮（NO）生成的影响。此外，还研究了阿片类药物对 LPS 刺激后 C8-B4 小胶质细胞吞噬作用的影响。
方法
用脂多糖（LPS）和干扰素-γ（IFN-γ）刺激 C8-B4 小鼠小胶质细胞后，用不同浓度的阿片类药物处理。测定亚硝酸盐的产生。通过 Western 印迹法测定 iNOS 和 Cox-2，并用荧光免疫染色法评估在 LPS 激活后用阿片类药物培养的总小胶质细胞中吞噬荧光微球的小胶质细胞的百分比。
结果
在 LPS 和 IFN-γ刺激后，小胶质细胞产生的一氧化氮（NO）产量较低，布比卡因、萨利沃林 A 和纳洛酮（P<0.05）。与纳洛酮联合使用时，与布比卡因相比没有显著差异。结果表明，布比卡因和萨利沃林 A 可以抑制 LPS 和 IFN-γ激活的 iNOS 表达。LPS 刺激后吞噬作用大大增加，添加萨利沃林 A 后观察到明显增加。
结论
布比卡因和萨利沃林 A 可降低 LPS 和 IFN-γ激活的小胶质细胞中 NO 产生和 iNOS 诱导。萨利沃林 A 促进了 LPS 处理的小胶质细胞的吞噬作用。
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