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目的探索钙卫蛋白(S100A8/A9)、Toll样受体4(TLR-4)及丝裂原活性的蛋白激酶(MAPK)信号传导途径在动脉血栓中的表达及与环氧化酶-2(COX-2)的关系。方法 24只SD大鼠分为实验组和对照组,实验组利用FeCl_3溶液建立颈动脉血栓大鼠模型,对照组注射等量生理盐水。分别于造模后第1、3、7、14日分批处死2组大鼠,每次每组3只。利用ELISA检测大鼠外周血S100A8/A9水平。采用Western blotting对SD大鼠外周血白细胞中COX-2、p-p38 MAPK、TLR-4水平进行检测,并分析各因子水平之间的相关性。利用MAPK抑制剂SB203580对模型大鼠进行干预,观察对COX-2蛋白水平的影响。结果实验组大鼠外周血S100A8/A9水平在造模后第7日达到最高值,第14日回落,且均显著高于对照组相应时间点水平(P<0.05)。外周血白细胞中TLR-4、p-p38 MAPK、COX-2的表达水平随造模后时间的推移逐渐升高,第14日达到最高值。其中TLR-4与COX-2之间相关性较好(r=0.831,P=0.012)。模型大鼠经MAPK抑制剂干预后,COX-2蛋白水平显著降低。结论 S100A8/A9可能主要参与动脉形成早期炎症反应过程,COX-2与TLR-4在蛋白水平的表达具有一定相关性。动脉血栓形成初期COX-2表达升高可能与体内高水平S100A8/A9激活TLR-4/p38 MAPK信号途径调节有关。
Objective To explore the expression of calpastatin (S100A8 / A9), Toll-like receptor 4 (TLR-4) and mitogen-activated protein kinase (MAPK) signaling pathway in arterial thrombosis and its relationship with cyclooxygenase- COX-2). Methods Twenty-four SD rats were divided into experimental group and control group. In the experimental group, carotid artery thrombosis rat model was established by using FeCl_3 solution. The control group was injected with normal saline. Two groups of rats were killed in batches on the 1st, 3rd, 7th and 14th days after the model was established, each with 3 rats in each group. The levels of S100A8 / A9 in peripheral blood of rats were detected by ELISA. Western blotting was used to detect the levels of COX-2, p-p38 MAPK and TLR-4 in peripheral blood leukocytes of SD rats, and the correlation between the levels of each factor was analyzed. The model rats were intervened by MAPK inhibitor SB203580 to observe the effect on the protein level of COX-2. Results The levels of S100A8 / A9 in the peripheral blood of rats in experiment group reached the highest value on the 7th day after the model was established, and dropped on the 14th day, all of which were significantly higher than those of the control group at the corresponding time points (P <0.05). The expression levels of TLR-4, p-p38 MAPK and COX-2 in peripheral blood leucocytes increased gradually with the passage of time, reaching the highest on the 14th day. The correlation between TLR-4 and COX-2 was better (r = 0.831, P = 0.012). After the intervention of MAPK inhibitor, the level of COX-2 protein in model rats was significantly decreased. Conclusion S100A8 / A9 may be mainly involved in the process of arterial formation of early inflammatory reaction. The expression of COX-2 and TLR-4 may be related to the protein level. The elevated COX-2 expression in the early stage of arterial thrombosis may be related to the regulation of TLR-4 / p38 MAPK signaling pathway by high levels of S100A8 / A9 in vivo.