發(fā)布時(shí)間：2019-06-20 09:41

【摘要】：前期研究發(fā)現(xiàn)AAMTS-18為血小板整合素GⅢIa49-66表位的生理配基,可激活“血小板內(nèi)ROS氧化通路”,使血小板氧化破碎并溶解血栓。我們推測ADAMTS-18有可能是人體自身分泌的一種調(diào)節(jié)動(dòng)脈血栓形成的蛋白。我們利用已構(gòu)建的ADAMTS-18基因敲除(KO)小鼠,比較其與相同背景的野生型(WT)小鼠之間血小板功能的差異及其在動(dòng)脈血栓形成中的作用。經(jīng)過流血時(shí)間檢測,血小板計(jì)數(shù)檢測,以及小鼠急性肺栓塞形成實(shí)驗(yàn),頸動(dòng)脈血栓形成實(shí)驗(yàn),短暫性腦中動(dòng)脈缺血再灌注(tMCAO)實(shí)驗(yàn)之后,我們發(fā)現(xiàn)ADAMTS-18缺失對(duì)小鼠血小板的功能及出凝血時(shí)間影響較小,但它卻對(duì)動(dòng)脈血栓的形成有著間接地影響。在三氯化鐵誘導(dǎo)的頸動(dòng)脈血栓形成模型上發(fā)現(xiàn)WT和KO小鼠頸動(dòng)脈血管發(fā)育存在顯著差異,KO小鼠頸動(dòng)脈提前分叉,血流速度較WT小鼠減慢(WT vsKO,0.75±0.21 vs 0.5±0.11 ml/min,P=0.0321),頸動(dòng)脈血栓形成時(shí)間較WT小鼠明前縮短(WT vs KO,611±92 vs 452±68 sec,P=0.005).此外,WT和KO小鼠頸動(dòng)脈小體存在明顯差別,絕大多數(shù)KO小鼠缺乏頸動(dòng)脈小體。隨后我們又發(fā)現(xiàn)KO小鼠較WT小鼠有更為明顯的腦梗塞損傷[WT(n=8)vs KO(n=7), 17.41±3.24 vs 25.68±4.13,P=0.0012].上述結(jié)果提示：ADAMTS-18有可能與頸動(dòng)脈血管及頸動(dòng)脈小體的發(fā)育有關(guān),從而間接影響動(dòng)脈血栓的形成。
[Abstract]:Previous studies have found that AAMTS-18 is the physiological ligand of platelet integrin G III Ia49-66 epitope, which can activate the "ROS oxidation pathway in platelets", make platelets oxidize and break up and dissolve thrombus. We speculate that ADAMTS-18 may be a protein secreted by the human body that regulates arterial thrombosis. We used the constructed ADAMTS-18 gene knockout (KO) mice to compare the difference of platelet function between the constructed (WT) mice and the wild type (WT) mice with the same background and its role in arterial thrombosis. After bleeding time test, platelet count test, acute pulmonary embolism test, carotid thrombosis test and transient middle cerebral artery ischemia-reperfusion (tMCAO) test, we found that ADAMTS-18 deletion had little effect on platelet function and coagulation time in mice, but it had an indirect effect on the formation of arterial thrombosis. In the model of carotid thrombosis induced by iron trichloride, there was significant difference in carotid artery development between WT and KO mice. The carotid artery of KO mice bifurcation ahead of time, the blood flow velocity of KO mice was slower than that of WT mice (WT vsKO,0.75 鹵0.21 vs 0.5 鹵0.11 ml/min,P=0.0321), and the time of carotid thrombosis was shortened by (WT vsKO, 611 鹵92 vs 452 鹵68 sec,P=0.005 than that of WT mice. In addition, there were significant differences in carotid corpuscles between WT and KO mice, and most KO mice lacked carotid corpuscles. Then we found that KO mice had more obvious cerebral infarction injury than WT mice [WT (n 鈮，

本文編號(hào)：2503121