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机构地区:[1]中山大学中山医学院药理学教研室
出 处:《Acta Pharmacologica Sinica》2003年第7期675-680,726,共7页中国药理学报(英文版)
基 金:Project supported by the National Natural Science Foundation of China, № 39670838.
摘 要:AIM: To observe the effects of activation of complements on platelets and subsequently on vascular endothelial cells (VEC) and vascular smooth muscle cells (VSMC). METHODS: Zymosan A-induced morphological change of platelets was determined with an aggregometer, and prothrombinase expression was quanitified using chromogenic substrate. Supernatant of zymosan A-treated platelet rich plasma (PRP) was added to the cultured VEC or VSMC for the observation of cell growth, DNA content, and the membrane microviscosity. RESULTS: Zymosan A induced marked metamorphosis, increased membrane microviscosity, and increased prothrombinase expression of platelets in PRP, but platelet metamorphosis induced by zymosan A was not found in washed platelets and fresh platelet suspended in platelet poor plasma (PPP) which had been pretreated with cobra venom factor (CVF). The effect of zymosan A on platelets was prevented by egtazic acid 5 mmol/L, Mn^(2+) 10 mmol/L, tetrodotoxin 40 μmol/ L or indomethacin 100μmol/L. The supernatant of zymosan A-treated PRP inhibited the growth of VEC, but accelerated the growth of VSMC and made most VSMC enter G_2-and M-phase. The endoplasmic reticulum with rough surface and free ribosome in VSMC and vacuoles appeared in VEC mitochondria. CONCLUSION: Activated complements induced significant shape change of platelets, stimulated platelets to release some factors and subsequently injured VEC, but accelerated the growth of VSMC, which may contribute to the development of blood coagulation and to the chronic inflammation.目的:研究激活补体对血小板的作用和随后对血管内皮细胞和血管平滑肌细胞的作用。方法:用酵母多糖A激活补体观察血小板变形、凝血活酶表达和膜粘度的改变,观察酵母多糖A处理的富血小板血浆对内皮细胞和血管平滑肌细胞的生长、DNA含量和膜微粘度的影响。结果:酵母多糖A能引起富血小板血浆的血小板明显变形、膜微粘度增加和凝血活酶表达增加,但不引起经洗脱的血小板变形,新鲜的贫血小板血浆能恢复酵母多糖A引起的作用,但经眼镜蛇毒因子预处理后作用消失,酵母多糖A引起的血小板变形能被依他酸5mmol/L、Mn^(2+) 10nmol/L、河豚毒素40μmol/L或吲哚美辛100μmol/L阻断,酵母多糖A处理的富血小板血浆上清液能抑制血管内皮细胞生长,但对血管平滑肌细胞生长有促进作用,促使血管平滑肌细胞进入G_2期和M期,同时内浆网变粗和游离的核糖体出现,而内皮细胞的线粒体出现空泡。结论:激活补体引起血小板显著变形,损伤血管内皮细胞并使血管平滑肌细胞增殖。
关 键 词:COMPLEMENT blood platelets ZYMOSAN vascular endothelium vascular smooth muscle
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