探讨重组人促红细胞生成素改善血管性痴呆大鼠认知功能的可能机制  

The Possible Mechanism of Recombinant Human Erythropoietin Improving the Cognitive Function in Rats with Vascular Dementia

作　　者：杨清洁[1] 郭军红[1] 

机构地区：[1]山西医科大学第一医院,硕士研究生太原030001

出　　处：《中西医结合心脑血管病杂志》2015年第17期1940-1943,共4页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：山西省科技厅科技攻关项目(No.2013011057-2)

摘　　要：目的研究重组人促红细胞生成素(rhEPO)改善血管性痴呆大鼠认知功能的可能作用机制。方法将30只清洁级雄性SD大鼠,经Morris水迷宫筛选合格后,随机分为5组:假手术组、2VO组、2VO+rhEPO组、2VO+rhEPO+AG490(JAK2抑制剂)组、2VO+AG490组,每组6只。结扎双侧颈总动脉(2VO)建立血管性痴呆模型。造模3 d后,各组分别腹腔给予AG490(5 mg/kg)或等剂量的二甲基亚砜(DMSO,AG490的溶媒),30 min后鼻腔给予rhEPO(150 U/125μL)或等量的生理盐水,每周给药1次,共8次。8周后行Morris水迷宫试验检测各组大鼠的空间学习及记忆能力。HE染色观察各组大鼠海马CA1区细胞形态学变化。结果行为学测试结果,定位航行,随着训练天数的增加,各组大鼠逃避潜伏期明显缩短。2VO+rhEPO组平均逃避潜伏期明显低于2VO组、2VO+rhEPO+AG490组、2VO+AG490组,差异均具有统计学意义(P<0.05),与假手术组比较差异无统计学意义(P>0.05)。空间探索实验:2VO+rhEPO组穿越平台次数明显高于2VO组、2VO+rhEPO+AG490组、2VO+AG490组,差异均有统计学意义(P<0.05)。HE染色结果:假手术组海马CA1区细胞排列整齐,细胞形态正常;2VO组海马CA1区细胞排列紊乱,可见胞体萎缩,核深染,核固缩,核溶解;2VO+rhEPO组:海马CA1区细胞排列相对整齐,细胞结构与正常细胞接近,偶见胞体缩小;2VO+rhEPO+AG490组、2VO+AG490海马CA1区细胞形态学改变与2VO组类似。结论经鼻腔给予rhEPO能改善血管性痴呆性大鼠的认知功能,其作用机制可能与激活JAK2/STAT3通路有关。Objective To investigate the possible mechanism of recombinant human erythropoietin （rhEPO） to improve the cognitive function in rats with vascular dementia. Methods By Morris water maze qualified after screening,thiry clean male Sprague- Dawley （SD＋ rats were randomly divided into five groups, Sham group, group 2（2VO group）, group 3（2VO ＋ rhEPO group）, group 42VO ＋ rhEPO＋ AG490（Janus kinase 2 inhibitor）group and group 5（2VO＋ AG490 group）. Six rats were in each group. The bilateral occlu- sion of common carotid arteries in SD rats was adopted to established the vascular dementia model. Rats respectively were disposed by intraperitoneal injection of AG490（5 mg/kg） or the same quantity of DMSO - AG490 solvent after chronic ischemia for 3 days. After 30 minutes, rats respectively undergone intranasal delivery rhEPO at the dose of 150 U/125 μL or equivalent volume of saline at the sametime and administered once a week for a total of eight times. After the 8 weeks , the Morris water maze was explored to ob- served the spatial learning and memory capability. Morphology changes of hippocampal CA1 nerve cells were observed by Hematox ylin-Eosin （HE） staining. Results Behavioral tests results showed that the mean escape latency, with the increase of training days,was significantly shortened in rats. The average escape latency period in group 3 was lower than that in group 2, group 4 and group 5（ P 〈0. 05）. The number of cross - platform in group 3 was obviously higher than that in group 2,group 4,group 5（ P 〈0. 05）. HE staining showed that cells were ordered in the hippocampal CA1 area and with normal cells form in Sham group. The cells of hipp ocampal CA1 area were disordered and the cell body contraction, nuclear hyperchromatic, nucleus pycnosis and nuclear dissolved could be visible in group2. The cells of hippocampal CA1 area arranged neatly and the cell structure closed to normal cells,a few of contractible cells could be seen occasionally in group 3. The morpholog

关 键 词：血管性痴呆 促红细胞生成素 JAK2-STAT3 AG490 

分 类 号：R749.13[医药卫生—神经病学与精神病学]