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疏水性而非亲水性他汀类药物在体外可增强人外周血细胞的吞噬作用并减少其凋亡。

Hydrophobic but not hydrophilic statins enhance phagocytosis and decrease apoptosis of human peripheral blood cells in vitro.

作者信息

Salman Hertzel, Bergman Michael, Djaldetti Meir, Bessler Hanna

机构信息

Department of Medicine C, Rabin Medical Center, Hasharon Hospital, the Sackler School of Medicine, Tel Aviv University, 7 Keren Kayemet Street, Petah Tiqva, Israel.

出版信息

Biomed Pharmacother. 2008 Jan;62(1):41-5. doi: 10.1016/j.biopha.2007.07.007. Epub 2007 Aug 9.

Abstract

The engulfing ability of phagocyting cells is related to the fluidity of the cell membrane that in turn depends on its chemical composition. Changes in membranal lipid content may increase or decrease membranal fluidity with a subsequent enhanced or impaired phagocytosis, respectively. Statins are recognized as potent inhibitors of cholesterol synthesis and therefore, are successfully administered to patients with hypercholesterolemia. Since it is considered that cholesterol affects cell function via changes in membrane composition, the present study was designed to examine the in vitro effect of three hydrophobic statins--atorvastatin, lovastatin and simvastatin, and a hydrophilic one--pravastatin, on the engulfing capacity, phagocytic index and apoptosis of peripheral blood phagocytes from healthy volunteers. Peripheral white blood cells obtained from 20 healthy normocholesterolemic individuals were incubated for 2h with 10 and 50 microM of the four statins and phagocytosis of fluorescent latex particles was detected by flow cytometry. Apoptosis was examined using annexin V and propidium iodide staining. An increase in the percentage of phagocyting cells was observed after incubation with 50 microM of lovastatin and simvastatin. On the other hand, all three hydrophobic statins induced a dose-dependent increase in the phagocytic index. The hydrophilic pravastatin did not affect phagocytosis, phagocytic index and apoptosis. All three hydrophobic statins at 50 microM exerted a slight, but significant decrease of apoptosis. The results suggest that the effect of hydrophobic statins on the engulfing capacity of human peripheral blood phagocytes and apoptosis is dependent on their dosage and physiochemical properties. This observation is an additional contribution to the statins' pleiotropic effect.

摘要

吞噬细胞的吞噬能力与细胞膜的流动性有关,而细胞膜的流动性又取决于其化学成分。膜脂质含量的变化可能会增加或降低膜的流动性,进而分别增强或损害吞噬作用。他汀类药物被认为是胆固醇合成的有效抑制剂,因此已成功应用于高胆固醇血症患者。由于人们认为胆固醇通过改变膜成分来影响细胞功能,本研究旨在检测三种疏水他汀类药物——阿托伐他汀、洛伐他汀和辛伐他汀,以及一种亲水他汀类药物——普伐他汀,对健康志愿者外周血吞噬细胞的吞噬能力、吞噬指数和凋亡的体外影响。从20名健康的正常胆固醇水平个体中获取外周血白细胞,分别与10微摩尔和50微摩尔的这四种他汀类药物孵育2小时,然后通过流式细胞术检测荧光乳胶颗粒的吞噬情况。使用膜联蛋白V和碘化丙啶染色检测细胞凋亡。用50微摩尔的洛伐他汀和辛伐他汀孵育后,观察到吞噬细胞百分比增加。另一方面,所有三种疏水他汀类药物均引起吞噬指数呈剂量依赖性增加。亲水性的普伐他汀不影响吞噬作用、吞噬指数和细胞凋亡。50微摩尔的所有三种疏水他汀类药物均使细胞凋亡略有但显著减少。结果表明,疏水他汀类药物对人外周血吞噬细胞吞噬能力和细胞凋亡的影响取决于其剂量和理化性质。这一观察结果为他汀类药物的多效性作用增添了新的内容。

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