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遗传性巨血小板减少性Wistar Furth大鼠血小板和巨核细胞中的脂质及膜流动性异常

Lipid and membrane fluidity abnormalities in platelets and megakaryocytes of the hereditary macrothrombocytopenic Wistar Furth rat.

作者信息

Dalal K B, Leven R M, Yee T

机构信息

Lawrence Berkeley Laboratory, University of California, Berkeley 94720.

出版信息

Biochim Biophys Acta. 1991 Nov 18;1070(1):253-8. doi: 10.1016/0005-2736(91)90172-5.

DOI:10.1016/0005-2736(91)90172-5
PMID:1751531
Abstract

Biochemical and functional abnormalities of megakaryocytes and platelets were studied in Wistar Furth (WF) rats which have genetically determined macrothrombocytopenia and megakaryocytopenia, and were compared with their counterparts in Sprague-Dawley (SD) rats. Both megakaryocytes and platelets synthesized phospholipids from [14C]acetate. WF and SD megakaryocytes incorporated 0.27 and 0.29 nmol acetate per 10(6) cells, respectively. Phosphatidylcholine (PC) accounted for 64% and 58% of the PL radioactive label in megakaryocytes of SD and WF rats, respectively, (P less than 0.05), while 69% of labeled activity was associated with PC of SD platelets compared to 60% found in PC of WF platelets (P less than 0.01). In WF platelets a significant increase in the levels of lysophosphatidylcholine (6.1% vs. 3.0%) was observed. WF platelets had substantially higher levels of esterified cholesterol, triglycerides, ceramides and a 3-fold increase in the total protein per platelet compared to SD platelets. The fatty acid composition of WF platelet PC showed quantitative abnormalities. Plasma lecithin-cholesterol acyl transferase activity and platelet function monitored by the uptake and release of [14C] serotonin showed nonsignificant variations between SD and WF rats. Compared with the control, platelet membrane fluidity, measured by fluorescence polarization using platelets labeled with 1,6-diphenyl-1,3,5-hexatriene, was significantly decreased in the WF rats.

摘要

在具有遗传性大血小板减少症和巨核细胞减少症的Wistar Furth(WF)大鼠中研究了巨核细胞和血小板的生化及功能异常,并与Sprague-Dawley(SD)大鼠的相应情况进行了比较。巨核细胞和血小板均能利用[14C]乙酸盐合成磷脂。WF和SD巨核细胞每10(6)个细胞分别摄取0.27和0.29 nmol乙酸盐。磷脂酰胆碱(PC)分别占SD和WF大鼠巨核细胞中磷脂放射性标记的64%和58%,(P<0.05),而SD血小板中69%的标记活性与PC相关,相比之下,WF血小板的PC中这一比例为60%(P<0.01)。在WF血小板中观察到溶血磷脂酰胆碱水平显著升高(6.1%对3.0%)。与SD血小板相比,WF血小板中的酯化胆固醇、甘油三酯、神经酰胺水平显著更高,且每个血小板的总蛋白增加了3倍。WF血小板PC的脂肪酸组成显示出定量异常。通过[14C]血清素的摄取和释放监测的血浆卵磷脂胆固醇酰基转移酶活性和血小板功能在SD和WF大鼠之间无显著差异。与对照组相比,使用1,6-二苯基-1,3,5-己三烯标记的血小板通过荧光偏振测量的WF大鼠血小板膜流动性显著降低。

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