新型金属蛋白酶ADAMTS-18在动脉血栓形成中的作用机制研究
发布时间：2019-06-20 09:41
【摘要】：前期研究发现AAMTS-18为血小板整合素GⅢIa49-66表位的生理配基,可激活“血小板内ROS氧化通路”,使血小板氧化破碎并溶解血栓。我们推测ADAMTS-18有可能是人体自身分泌的一种调节动脉血栓形成的蛋白。我们利用已构建的ADAMTS-18基因敲除(KO)小鼠,比较其与相同背景的野生型(WT)小鼠之间血小板功能的差异及其在动脉血栓形成中的作用。经过流血时间检测,血小板计数检测,以及小鼠急性肺栓塞形成实验,颈动脉血栓形成实验,短暂性脑中动脉缺血再灌注(tMCAO)实验之后,我们发现ADAMTS-18缺失对小鼠血小板的功能及出凝血时间影响较小,但它却对动脉血栓的形成有着间接地影响。在三氯化铁诱导的颈动脉血栓形成模型上发现WT和KO小鼠颈动脉血管发育存在显著差异,KO小鼠颈动脉提前分叉,血流速度较WT小鼠减慢(WT vsKO,0.75±0.21 vs 0.5±0.11 ml/min,P=0.0321),颈动脉血栓形成时间较WT小鼠明前缩短(WT vs KO,611±92 vs 452±68 sec,P=0.005).此外,WT和KO小鼠颈动脉小体存在明显差别,绝大多数KO小鼠缺乏颈动脉小体。随后我们又发现KO小鼠较WT小鼠有更为明显的脑梗塞损伤[WT(n=8)vs KO(n=7), 17.41±3.24 vs 25.68±4.13,P=0.0012].上述结果提示：ADAMTS-18有可能与颈动脉血管及颈动脉小体的发育有关,从而间接影响动脉血栓的形成。
[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 卤0.21 vs 0.5 卤0.11 ml/min,P=0.0321), and the time of carotid thrombosis was shortened by (WT vsKO, 611 卤92 vs 452 卤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，
本文编号：2503121
[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 卤0.21 vs 0.5 卤0.11 ml/min,P=0.0321), and the time of carotid thrombosis was shortened by (WT vsKO, 611 卤92 vs 452 卤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，
本文编号：2503121
本文链接：https://www.wllwen.com/yixuelunwen/shenjingyixue/2503121.html
最近更新
教材专著
