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Topiramate对宫内缺血大鼠脑组织含水量及神经细胞凋亡的影响
目的:观察topiramate对宫内急性脑缺血损伤的Wistar大鼠神经细胞凋亡及脑组织含水量的影响.方法 : 夹闭足月妊娠大鼠子宫血管,制成急性脑缺血损伤的新生鼠模型(n=315),随机分为topiramate 1次和5次给药组及缺血组(n=105),另取105只正常Wistar大鼠作为正常对照组.治疗组给予topiramate,观察脑缺血后再灌注3 h、6 h、24 h、3 d、7 d、14 d、21 d、28 d海马TUNEL法标记的凋亡神经细胞的变化及生后7 d内脑组织含水量的变化.结果 : topiramate 1次组脑组织含水量12和72 h显著低于缺血对照组,topiramate 5次组48和72 h显著低于缺血对照组及topiramate 1次组(P＜0.05);topiramate 1次组24 h、3 d、7 d、21 d 凋亡神经细胞数明显低于缺血对照组,topiramate 5次组3和7 d凋亡神经细胞数明显低于缺血对照组和topiramate1次组(P＜0.05).结论 : topiramate可以明显减少宫内急性脑缺血后新生大鼠神经细胞的凋亡数目,并可以缩短凋亡持续时间;延缓脑水肿的发生,减轻脑水肿的程度, 并缩短其持续时间,多次给药组的作用明显高于1次给药组.
关键词： 脑缺血 topiramate 抗惊厥药 脑水肿 细胞凋亡 -
托吡酯对Lewis肺癌转移的抑制作用与水通道蛋白1的关系
AIM: To study the effect of topiramate on tumor metastasis and its relation with aquaporin 1 (AQP1) water channel. METHODS: Lewis lung carcinoma metastatic model was used to determine the effect of topiramate on tumor growth and metastasis. Colorimetric estimation was used to investigate the action of topiramate on carbonic anhydrase (CA) activity. Western blotting and immunohistochemical analysis were used to study the influence of topiramate on AQP1 water channel expression in lungs or tumor tissues of mice bearing Lewis lung carcinoma.cantly (P＜0.05). Its inhibitory rate of metastasis was 81.25 %. Topiramate inhibited CA activity in lungs of mice in a dose-dependent manner. Topiramate apparently decreased AQP1 protein expression and immunostaining in lungs or in tumor microvessel endothelial cells of mice. CONCLUSION: Suppression of AQP1 water channel expression may be an important pathway for the inhibitory effect of topiramate on tumor metastasis.
