Inhibition of cyclooxygenase 2 by nimesulide decreases prostaglandin E2 formation but does not alter brain edema or clinical recovery after closed head injury in rats
Inhibition of cyclooxygenase 2 by nimesulide decreases prostaglandin E2 formation but does not alter brain edema or clinical recovery after closed head injury in rats
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DOI：
10.1097/00008506-200001000-00009
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发表时间：
2000-01-01
影响因子：
3.7
通讯作者：
Shapira, Y
中科院分区：
文献类型：
--
作者：
Koyfman, L;Kaplanski, J;Shapira, Y
近年来，环氧合酶（考克斯）被认为存在组成型（考克斯-1）和诱导型（考克斯-2）。在以前的研究中，药物chat是考克斯-1和考克斯-2的抑制剂，不能减少脑水肿的形成或改善闭合性头部创伤（CHT）后的神经系统严重程度评分（NSS），尽管有些药物确实减少了前列腺素E2（PGE 2）的形成。本研究探讨了考克斯-2（尼美舒利）的特异性抑制剂是否在大鼠CHT后发挥有益作用。将氟烷麻醉的大鼠（每组n = 8）随机分为四组：手术，无CHT，无药物（第1组）;手术，无CHT，腹腔注射尼美舒利30 mg/kg（IP）（第2组）;手术，CHT，无药物（第3组）;手术，CHT，尼美舒利30 mg/kg IP（第4组）。于处死后1、24 h测定NSS，24 h测定脑组织PGE 2浓度和含水量。尼美舒利治疗未改善NSS（第3组24 h NSS = 11 +/- 6 [中位数+/-范围]，第4组12 +/- 4）或水肿形成（第3组24 h脑含水量= 84.3 +/- 1.8% [平均值+/- SD]，第4组83.8 +/- 1.9%）。然而，尼美舒利降低皮质和下丘脑PGE？在脑组织取样后孵育的第一个小时内，形成分别为41%和47%。作者得出结论，尽管尼美舒利确实减少了组织PGE 2的形成，但它对大鼠CHT后的脑组织水肿或功能活动没有产生有益的影响。
Recently, the enzyme cyclooxygenase (COX) has been recognized to exist as constitutive (COX-1) and inducible isoforms (COX-2). In previous studies, drugs chat were inhibitors of both COX-1 and COX-2 failed to decrease brain edema formation or improve Neurological Severity Score (NSS) after closed head trauma (CHT), although some did decrease prostaglandin-E2 (PGE2) formation. The present study examined whether or not a specific inhibitor of COX-2 (nimesulide) exerts a beneficial effect after CHT in rats. Halothane-anesthetized rats (n = 8 in each group) were randomly assigned to one of four groups: surgery, no CHT, no drug (group 1); surgery, no CHT, nimesulide 30 mg/kg intraperitoneally (IP) (group 2); surgery, CHT, no drug (group 3); and surgery, CHT, nimesulide 30 mg/kg IP (group 4). NSS was determined at 1 and 24 h, and brain tissue PGE2 concentration and water content were determined after killing at 24 h. Treatment with nimesulide did not improve NSS (NSS at 24 h = 11 +/- 6 [median +/- range] in group 3 and 12 +/- 4 in group 4) or edema formation (brain water content at 24 h = 84.3 +/- 1.8% [mean +/- SD] in group 3 and 83.8 +/- 1.9% in group 4). However, nimesulide did decrease cortical and hypothalamic PGE? formation by 41% and 47%, respectively during the first hour of incubation after brain tissue sampling. The authors conclude that although nimesulide does reduce tissue PGE2 formation, it does not exert a beneficial effect on brain tissue edema or functional activity after CHT in rats.