Aliskiren预处理对脑缺血再灌注损伤的保护及对脑能量代谢的影响  

The protective effect on cerebral ischemia.reperfusion injury and influence on brain energy metabolism of aliskiren pretreatment

作　　者：张涛[1] 法志强[2] 郭燕舞[2] 

机构地区：[1]天津市环湖医院重症医学科,300060 [2]南方医科大学珠江医院神经外科

出　　处：《中华神经外科杂志》2013年第6期626-631,共6页Chinese Journal of Neurosurgery

基　　金：国家自然科学基金（30901546/H0912）

摘　　要：目的探讨Aliskiren预处理对脑缺血再灌注（I／R）损伤的保护作用及对脑能量代谢的影响。方法将雄性ICR小鼠随机分为假手术组（Sham组）、溶剂对照组（Vehicle组）、低剂量Aliskiren预处理组（Alis．L组）和高剂量Aliskiren预处理组（Alis—H组）；采用Zea—longa改良线栓法大脑中动脉闭塞（MCAO）制备局灶性脑I／R模型，于I／R24h后采用r137C染色法评估脑梗死面积、DHE染色观察脑活性氧自由基水平、乳酸及Na’．K’．ATPase检测试剂盒检测脑组织中乳酸水平及Na＋-K＋-ATPase活性；于I／R72h后腹腔注射Brdu检测海马DG区的神经细胞增殖情况；于I／R后不同时间采用神经行为学评分评价神经损伤情况，Morris水迷宫评价空间记忆能力。结果与Sham组相比，Vehicle组出现明显的梗死区域，梗死面积和梗死面树前脑面积均增加，脑活性氧自由基和乳酸水平升高，Na’．K’-ATPase活性降低，I／R后1—6d的神经行为学评分均降低，Morris水迷宫的逃避潜伏期延长，游泳速度减慢，海马DG区的BrdU’细胞数减少，差异均有统计学意义（P〈0．05）；Aliskiren预处理可改善Vehicle组的各指标变化，差异均有统计学意义（P〈0．05）。Alis-H组以上I／R导致的异常改善程度高于Alis．L组，差异均有统计学意义（P〈0．05）。结论Aliskiren预处理对脑缺血再灌注损伤有保护作用，并改善脑能量代谢情况。Objective To explore the protective effect on cerebral ischemia-reperfusion injury and i its influence on brain energy metabolism of aliskiren pretreatment. Methods Male ICR mice were randomly divided into the Sham group, Vehicle group, Alis-L group, and Alis-H group. The focal cerebral ischemia-reperfusion （I/R） model was induced by Zea-longa modified-suture middle cerebral artery occlusion （MCAO）. The cerebral infarction area was assessed by TYC staining, the reactive oxygen radical level observed by DHE staining, and the lactic acid and activity of Na ＋-K ＋ -ATPase measured by kits were all recorded at 24 h after I/R. Intraperitoneal injection of BrdU to detect the proliferation of nerve ceils in hippocampal DG was performed at 72 h after I/R. The nerve damage evaluated by neurological behavior score and spatial memory ability,assessed by the Morris water maze,were carried out at different times after I/R. Results Compared with the Sham group, there were obvious infarction areas, increased infarct size and infarct size/forebrain area, elevated oxygen free radicals and lactic acid levels, reduced activity of Na＋ - K ＋ -ATPase, decreased neurological behavior scores at 1 -6 days after I/R, the extended escape latency of Morris water maze and decreased BrdU cells in hippocampal DG region in the Vehicle group with significant differences （ P 〈 0.05）. The pretreatment of aliskiren can attenuate the changes in the Vehicle group with significant differences （ P 〈 0. 05）. The Alis-H group of the above I/R lead to the abnormal degree of improvement than the Alis-L group （ P 〈 0.05）. Conclusions Aliskiren pretreatment showed a protection effect on the cerebral ischemia-reperfusion iniurv and influenced brain energy metabolism.

关 键 词：ALISKIREN 脑缺血再灌注损伤 能量代谢 细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]