NF-κB抑制剂PDTC保护全脑缺血/再灌注大鼠海马损伤机制涉及COX2-PGI2/TXA2通路的初探  

COX2-PGI_2/TXA_2 signal pathway involved in protective mechanism of PDTC pretreatment against global cerebral ischemia reperfusion rat hippocampus injury

作　　者：王佳[1] 杨俊卿[1] 余丽娟[1] 杨彬[1] 赵磊[1] 蒋青松[1] 

机构地区：[1]重庆医科大学药理学教研室,重庆医科大学生物化学与分子药理学重点实验室,重庆400016

出　　处：《中国药理学通报》2014年第6期782-786,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81100905)

摘　　要：目的探讨NF-κB抑制剂PDTC预处理对全脑缺血/再灌注大鼠海马损伤的作用及机制。方法♂SD大鼠随机分为4组,即假手术组、全脑缺血/再灌注组(GCIR组)、PDTC 100和200 mg·kg-1组(P100组、P200组)。采用夹闭双侧颈总动脉合并低血压法建立全脑缺血/再灌注模型。P100组和P200组在缺血前1 h分别给予100或200 mg·kg-1腹腔注射,假手术组及GCIR组给予等容积的生理盐水。Morris水迷宫检测空间学习记忆能力,HE染色观察大鼠海马神经元形态及数目改变,Western blot检测COX2蛋白表达,ELISA测定大鼠海马中PGI2、TXA2含量。结果 GCIR组大鼠寻台潜伏期比假手术组明显延长(P<0.05),P100组和P200组与GCIR组比较明显缩短;P100组和P200组大鼠海马CA1区神经元核固缩减少,细胞死亡百分率比GCIR组明显减少(P<0.05);PDTC抑制全脑缺血/再灌注大鼠海马COX2蛋白表达,降低PGI2/TXA2比值。结论 PDTC对全脑缺血/再灌注大鼠海马损伤具有保护作用,其机制可能涉及抑制NF-κB,下调COX2蛋白表达,降低PGI2/TXA2比值。Aim To investigate the effects and mecha-nism of nuclear factor-κ B inhibitor, PDTC, on global cerebral ischemia reperfusion （ GCIR ） rat hippocam-pus. Methods Forty-eight adult male Sprague-Daw-ley rats were randomly divided into one control group receiving sham operation and three experimental groups all receiving global cerebral ischemia for 20 min. In PDTC 100 mg·kg-1 group （ P100 ） and PDTC 200 mg ·kg-1 group （ P200 ） , PDTC 100 mg · kg-1 or PDTC 200 mg·kg-1 was injected ip one hour before ischemi-a respectively. Spatial learning and memory function of rats were tested using Morris water maze. HE staining was employed to observe pathological changes of hipp-ocampal neurons. Expression of COX2 was measured by Western blot, and the content of PGI2 and TXA2 in rat hippocampus was detected by enzyme-linked immu-nosorbent assay. Results A significant increase of es-cape latency was observed in GCIR group compared to the sham operation group（P〈0.05）. PDTC 100 mg· kg-1 and PDTC 200 mg · kg-1 significantly reduced escape latency （ P 〈0.05 ） and histopathological injury in CA1 region of hippocampus. PDTC 100 mg · kg-1 and PDTC 200 mg · kg-1 also reduced COX2 expres-sion, PGI2 content, TXA2 content and PGI2/TXA2 . Conclusion Pretreatment with PDTC can protect hip-pocampus from GCIR injury through inhibition of COX2 expression and PGI2/TXA2 .

关 键 词：全脑缺血 再灌注 海马 NF-ΚB COX2 PDTC 前列环素 血栓素A2 

分 类 号：R-332[医药卫生] R322.81