抑制AMP-活化蛋白激酶对局灶性脑缺血再灌注小鼠缺血皮质胱天蛋白酶-3表达和细胞凋亡的影响  

Effects of inhibition of adenosine monophosphate-acfivated protein kinase on caspase-3 expression and apoptosis in ischemic cortex of focal cerebral ischemia-reperfusion in mice

作　　者：赵卫华[1] 苏玲[2] 郭再玉[1] 张合亮[1] 杨国巍[1] 田思思[3] 李博[1] 张青燕[4] 李绍山[5] 

机构地区：[1]天津市泰达医院神经外科,300457 [2]天津市泰达医院麻醉科,300457 [3]天津市泰达医院神经内科,300457 [4]首都医科大学三博脑科医院神经内科,北京100093 [5]新疆医科大学第一附属医院神经外科,乌鲁木齐830054

出　　处：《国际脑血管病杂志》2015年第7期522-525,共4页International Journal of Cerebrovascular Diseases

基　　金：天津市滨海新区联合攻关科技项目（津20080831）

摘　　要：目的探讨抑制AMP-活化蛋白激酶（AMP．Activatedproteinkinase，AMPK）活性对小鼠脑缺血再灌注后胱天蛋白酶（caspase）-3表达和神经细胞凋亡的影响。方法36只雄性C57BL／6小鼠，按随机数字表法分为假手术组、缺血再灌注组和AMPK抑制剂组，每组12只。线栓法建立小鼠大脑中动脉闭塞模型，AMPK抑制剂组在插入线栓时腹腔注射AMPK抑制剂CompoundC（20mg／kg），假手术组和缺血再灌注组在相同时间点腹腔注射等体积生理盐水。脑缺血再灌注24h后应用免疫组化染色法检测胱天蛋白酶-3表达水平，应用TUNEL法检测神经细胞凋亡。结果AMPK抑制剂组皮质胱天蛋白酶一3阳性细胞[（7．16±5．85）个／高倍视野对（14．36±7．85）个／高倍视野；t=2．548，P=0．018]和TUNEL阳性细胞[（58．86±9．65）个／高倍视野对（81．00±12．21）个／高倍视野；t=4．928，P〈0．001]数量均显著少于缺血再灌注组。结论抑制AMPK活性可下调脑缺血再灌注后缺血皮质胱天蛋白酶一3表达，减少神经细胞凋亡。Objective To investigate the, effects of inhbition of adenosine monophosphate-activated protein kinase （AMPK） activity on caspase-3 expression and neuronal apoptosis after cerebral ischemia- reperfusion in mice. Methods A total of 36 male C57BL/6 mice were randomly divided into a sham operation group, an ischemia-reperfusion group and an AMPK inhitor group （n = 12 in each group）. A model of middle cerebral artery occlusion （MCAO） was induced by the suture method. AMPK inhitor Compound C （20 mg/kg） was injected intraperitoneally while inserting sutures in the AMPK inh^itor group. The equivalent volumes of normal saline solution was injected intraperitoneally at the same time points in the sham operation group and the ischemia-reperfusion group. At 24 h after cerebral ischemia-reperfusion, immunohistochemical staining was use to detect the expression levels of caspase-3. TUNEL method was used to detect neuronal apoptosis in mice. Results Compared with the ischemia-reperfusion group, the numbers of the cortical caspase-3 positive cells （7. 16 ±5.85 vs. 14. 36 ±7. 85; t =2. 548, P =0. 018） and the TUNEL positive cells （58.86±9. 65 vs. 81.00 ± 12.21; t =4. 928, P 〈0. 001） per high-power field in the AMPK inhitor group were decreased significantly. Conclusions Inhition of AMPK activity downregulates the expression of caspase-3 after cerebral ischemia-reperfusion, and reduces neuronal apoptosis.

关 键 词：脑缺血 再灌注损伤 AMP-活化蛋白激酶 胱天蛋白酶3 细胞凋亡 小鼠 

分 类 号：R743[医药卫生—神经病学与精神病学]