Zhu Han-yi, Bin Juan, Wang Chuang, Lin Huan-bing, Zhou Heng, Xu Jiang-ping
Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2011 Nov;31(11):1858-62.
To investigate the effect of piperphentonamine hydrochloride (PPTA) on cognitive deficits induced by ischemia-reperfusion and explore the possible mechanisms.
SD rats were randomly divided into sham-operated group, ischemia-reperfusion group (with saline injection), PPTA-treated groups (2.5, 5, 10 mg/kg) and edaravone-treated group (6 mg/kg). Cerebral ischemia-reperfusion injury was induced by middle cerebral artery occlusion, and the agents were administrated 1 h after ischemia. At 24 h after ischemia, step-through passive avoidance test was carried out, and 24 h later IL-1β, TNF-α, caspase-3 and HSP-70 mRNA expressions in the ischemic brain tissues were measured with RT-PCR.
In the step-through passive avoidance test, the rats in the ischemia-reperfusion group showed significantly shorter latency and more error times than those in the sham group, and these behavioral changes were improved significantly by treatments with PPTA and edaravone. Cerebral ischemia-reperfusion caused significantly increased expressions of IL-1β, TNF-α, caspase-3 and HSP-70 mRNA, and these changes were obviously reversed by PPTA, but not by edaravone.
PPTA can reverse cognitive deficits induced by cerebral ischemia-reperfusion probably by decreasing the inflammatory responses and cell apoptosis in the brain, suggesting its potential as a new therapeutic agent for improving the cognitive function following cerebral ischemia-reperfusion.
研究盐酸哌苯他明（PPTA）对缺血再灌注所致认知功能障碍的影响，并探讨其可能机制。
将SD大鼠随机分为假手术组、缺血再灌注组（注射生理盐水）、PPTA治疗组（2.5、5、10mg/kg）和依达拉奉治疗组（6mg/kg）。采用大脑中动脉闭塞法诱导脑缺血再灌注损伤，缺血1小时后给予相应药物。缺血24小时后进行穿梭箱被动回避试验，24小时后采用RT-PCR法检测缺血脑组织中IL-1β、TNF-α、caspase-3和HSP-70 mRNA的表达。
在穿梭箱被动回避试验中，缺血再灌注组大鼠的潜伏期明显缩短，错误次数明显增多，与假手术组相比差异有统计学意义；PPTA和依达拉奉治疗可显著改善这些行为变化。脑缺血再灌注导致IL-1β、TNF-α、caspase-3和HSP-70 mRNA表达显著增加，PPTA可明显逆转这些变化，而依达拉奉则无此作用。
PPTA可能通过减轻脑内炎症反应和细胞凋亡来逆转脑缺血再灌注所致的认知功能障碍，提示其作为改善脑缺血再灌注后认知功能的新型治疗药物具有潜在价值。
