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[腹膜巨噬细胞功能的调节:特定药物对其活性及精子吞噬作用的影响]

[Modulation of peritoneal macrophage function: effect of selected drugs on their activity and sperm phagocytosis].

作者信息

Kurzawa R

机构信息

Z Katedry i Zakładu Histologii i Embriologii Pomorskiej Akademii Medycznej w Szczecinie, Szczecin.

出版信息

Ann Acad Med Stetin. 1997;43:79-97.

PMID:9471925
Abstract

Leukocytes and their products (free oxygen radicals, cytokines, nitrogen intermediates and prostanoids) are considered to be the major etiopathological factors of male and female infertility. Particular attention is paid to macrophages, which play a crucial role in pathogenesis of infertility. They may modulate immunological response which is often directed towards spermatozoa, decreasing their ability to move, and fertilize egg cells. Spermatozoa are often phagocytosed by the macrophages. The immune cells may also damage egg cells and embryos, or even impair implantation. The aim of the work was to verify the influence of potentially immunomodulating drugs: nifedipine, danazol and acetylsalicylic acid on the activity of peritoneal macrophages. Mouse peritoneal macrophages were cultured with the studied drugs and spermatozoa. It was assumed that the production and release of tumor necrosis factor-alpha, nitrates and prostaglandin F2 alpha were indicative of the increased activity of the macrophages. Biochemical studies were correlated with the morphological ones conducted under transmission and scanning electron microscopes. These studies covered the morphology of the cells as well as the sperm phagocytosis by the macrophages. Nifedipine was found to decrease the release of nitrites and TNF alpha by the peritoneal macrophages (Tab. 1, 4, 5). The inhibitory effect was dose and time dependent. Nifedipine caused morphological changes which correlated with the decreased activity of the cells (Fig. 3, 4). The macrophages were round with short protrusions surrounding the spermatozoa. There were numerous endocytic vesicles in the cytoplasm of the macrophages. Danazol did not exert any effect on the activity of the studied peritoneal macrophages (Tab. 2, 4, 5). At higher concentration, a decreased release of nitrites and TNF alpha was noted. This correlated with necrotic changes in the scanning and transmission electron microscopes (Fig. 5, 6). The changes were seen in the studied macrophages and spermatozoa. The sperm phagocytosis was completely abolished. The acetylsalicylic acid had an inhibitory effect on the release of nitrites, PGF2 alpha and TNF alpha (Tab. 3, 4, 5). The effect was dose, and time dependent. It was not noted in the concentration lower than therapeutical. Acetylsalicylic acid did not cause any morphological changes, but the phagocytosis was inhibited (Fig. 7, 8). The experiments were to verify new potential possibilities of infertility treatment, particularly those depending on the malfunction of the immunological system.

摘要

白细胞及其产物(游离氧自由基、细胞因子、氮中间体和前列腺素)被认为是男性和女性不孕症的主要病因病理因素。巨噬细胞受到特别关注,它们在不孕症的发病机制中起关键作用。它们可能调节通常针对精子的免疫反应,降低精子的运动能力和使卵细胞受精的能力。精子经常被巨噬细胞吞噬。免疫细胞也可能损害卵细胞和胚胎,甚至损害着床。这项工作的目的是验证潜在的免疫调节药物:硝苯地平、达那唑和乙酰水杨酸对腹膜巨噬细胞活性的影响。将小鼠腹膜巨噬细胞与研究药物和精子一起培养。假设肿瘤坏死因子-α、硝酸盐和前列腺素F2α的产生和释放表明巨噬细胞活性增加。生化研究与在透射和扫描电子显微镜下进行的形态学研究相关。这些研究涵盖了细胞的形态以及巨噬细胞对精子的吞噬作用。发现硝苯地平可降低腹膜巨噬细胞亚硝酸盐和TNF-α的释放(表1、4、5)。抑制作用呈剂量和时间依赖性。硝苯地平引起形态学变化,这与细胞活性降低相关(图3、4)。巨噬细胞呈圆形,有围绕精子的短突起。巨噬细胞的细胞质中有许多内吞小泡。达那唑对所研究的腹膜巨噬细胞活性没有任何影响(表2、4、5)。在较高浓度下,观察到亚硝酸盐和TNF-α的释放减少。这与扫描和透射电子显微镜下的坏死变化相关(图5、6)。在所研究的巨噬细胞和精子中都观察到了这些变化。精子吞噬作用完全消失。乙酰水杨酸对亚硝酸盐、PGF2α和TNF-α的释放有抑制作用(表3、4、5)。该作用呈剂量和时间依赖性。在低于治疗浓度时未观察到该作用。乙酰水杨酸未引起任何形态学变化,但吞噬作用受到抑制(图7、8)。这些实验旨在验证不孕症治疗的新的潜在可能性,特别是那些取决于免疫系统功能障碍的可能性。

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