血栓素及血栓素受體路徑的激活會導致動脈攣縮、血小板粘附作用。本實驗嘗試利用基因剔除小鼠來驗證缺血再灌流損傷對血管失能的影響。
實驗方法及結果：由靜脈注射生理食鹽水、內皮素、U46619（血栓素合成酶激動劑），用野生型和三種不同基因剔除小鼠以心肌缺血再灌流損傷模式的研究。評估心臟表面的微循環及心電圖變化。心臟受損評估使用心肌滲透率丶troponin I濃度及心肌梗塞的面積。並測量血栓素合成酶、血栓素受體、內皮一氧化氮合成酶丶NADPH oxidase4 菸鹼醯胺腺嘌呤二核苷酸磷酸氧化酶4、介白素1β丶細胞凋亡蛋白含量以及冠循環流出液中的血栓素B2，過氧陰離子、一氧化氮濃度。並使用各種激活劑及拮抗劑於小鼠腸繋膜動脈血管肌做血管張力測試實驗。並使用氯化鐵於活體小鼠做螢光血小板粘附試驗。B6小鼠在缺血再灌流實驗中，明顯提升ST波段上揚高度，心肌組織的下述蛋白含量提高：血栓素合成酶、血栓素受體丶NADPH oxidase4 菸鹼醯胺腺嘌呤二核苷酸磷酸氧化酶4、介白素-1β丶細胞凋亡蛋白含量、血栓素B2，過氧陰離子釋放和心肌梗塞面積增加。而減少了內皮一氧化氮合成酶、一氧化氮濃度，並減少了心臟表面的微循環。這些效應在剔除基因小鼠TXAS–/–, TP–/– , TXAS–/–TP–/–或是服用阿斯匹靈小鼠獲得重要的緩解。服用阿斯匹靈及基因TXAS, TP和TXAS/TP的剔除，可以明顯緩解血管攣縮劑及血管擴張劑所造成血管張力的劇烈變化及在腸繫膜動脈在氯化鐵刺激下的血小板粘附用。
結論：抑制血栓素合成酶及血栓素受體訊息路徑可以獲得心臟及腸繫膜動脈對抗氧化壓力損傷的血管保護作用。

Objective: Activation of thromboxane A2 synthase (TXAS)/thromboxane A2 (TXA2)/ thromboxane prostanoid (TP) receptor leads to arterial constriction, platelet aggregation and vascular injury. We attempted to characterize the microvascular dysfunction in ischemia/reperfusion injury using genetically modified TXAS–/–, TP–/– and TXAS–/– TP–/– mice.
Approach and Results: The cardiac micro-circulation and electrocardiograms were evaluated from B6, TXAS–/–, TP–/– and TXAS–/– TP–/– mice in response to intravenous saline, endothelin-1, U46619 ( a TXA2 agonist ) and myocardial ischemia/reperfusion injury. Cardiac function was investigated with myocardial permeability, the troponin I, concentration and the infarct size. Myocardial TXAS, TP, endothelial nitric oxide synthase (eNOS), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOx4), 4-hydroxynonenal, interleukin (IL)-1β, cell apoptosis, coronary effluent thromboxane B2 (TXB2) and superoxide anions (O2–) and NO concentrations were measured. Mice mesenteric reactivity in response to various drugs was assessed by wire myography. In vivo fluorescent platelet adhesiveness to the mesenteric arterial endothelium after FeCl3 stimulation was examined. In B6 mice, ischemia/reperfusion significantly increased levels of ST-segment elevation, myocardial TXAS, TP, NOx4, IL-1β, apoptosis, coronary endothelin-1, TXB2, O2– release and the infarct size, with concomitant decreases in eNOS, NO concentrations and cardiac micro-circulation. These effects were remarkably depressed in TXAS–/–, TP–/– and TXAS–/– TP–/– mice. Aspirin treatment or depletion of the TXAS, TP or TXAS/TP gene significantly attenuated the exaggerated vascular reactivity by vasoconstrictors and vasodilators and efficiently reduced platelet adhesion to the mesenteric endothelium under FeCl3 stimulation.
Conclusion: Inhibiting TXAS/TXA2/TP signalling confers microvascular protection against oxidative injury in both cardiac and mesenteric arteries.

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