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氯米帕明,一种三环抗抑郁药,和司来吉兰,一种单胺氧化酶-B 抑制剂,经口服给药后调节小鼠吞噬细胞的活性。

Clomipramine, a tricyclic antidepressant, and selegiline, a monoamine oxidase-B inhibitor, modulate the activity of phagocytic cells after oral administration in mice.

机构信息

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.

出版信息

J Pharm Pharmacol. 2020 Jun;72(6):836-842. doi: 10.1111/jphp.13251. Epub 2020 Mar 7.

Abstract

OBJECTIVES

Our aim was to find out whether clomipramine, a tricyclic antidepressant, and selegiline, a monoamine oxidase-B inhibitor, influence the activity of phagocytic cells after in-vivo administration in mice.

METHODS

Clomipramine and selegiline were administered to Balb/c mice orally at a dose of 1 mg/kg, 7 or 14 times. IL-1β and nitric oxide (NO) levels were measured in supernatants of the peritoneal macrophage cultures stimulated in vitro with lipopolysaccharide from Escherichia coli. The phagocytic activity of the granulocytes and monocytes was determined using a commercial Phagotest 24 and 72 h after the last dose of the investigated drugs.

KEY FINDINGS

Seven doses of clomipramine or selegiline decreased IL-1β production, while a rise in its synthesis was observed after 14 doses of selegiline. Clomipramine administered 14 times increased NO production. Clomipramine and selegiline administered seven times reduced the percentage of phagocytosing granulocytes. The drugs administered 14 times increased the percentage of phagocytosing granulocytes and decreased the percentage of phagocytosing monocytes.

CONCLUSIONS

Both clomipramine and selegiline administered in vivo changed the phagocytic activity of blood cells and IL-1β and NO production by murine peritoneal macrophages. This effect depended on the drug, the number of doses and the type of phagocytic cells.

摘要

目的

我们旨在研究三环抗抑郁药氯米帕明和单胺氧化酶-B 抑制剂司来吉兰在体内给药后是否会影响小鼠吞噬细胞的活性。

方法

将氯米帕明和司来吉兰以 1mg/kg 的剂量口服给予 Balb/c 小鼠,共 7 或 14 次。用大肠杆菌脂多糖体外刺激腹膜巨噬细胞培养物,测量上清液中的白细胞介素-1β(IL-1β)和一氧化氮(NO)水平。在最后一次研究药物给药后 24 和 72 小时,使用商业 Phagotest 测定粒细胞和单核细胞的吞噬活性。

主要发现

氯米帕明或司来吉兰给药 7 次可降低 IL-1β的产生,而司来吉兰给药 14 次可观察到其合成增加。氯米帕明给药 14 次可增加 NO 的产生。氯米帕明和司来吉兰给药 7 次可降低吞噬性粒细胞的百分比。这些药物给药 14 次可增加吞噬性粒细胞的百分比并降低吞噬性单核细胞的百分比。

结论

体内给予的氯米帕明和司来吉兰均可改变血细胞的吞噬活性以及小鼠腹膜巨噬细胞产生的白细胞介素-1β(IL-1β)和一氧化氮(NO)。这种作用取决于药物、给药次数和吞噬细胞的类型。

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