c-Jun氨基末端激酶在慢性低O_2高CO_2大鼠海马损伤中的作用  

Role of c-Jun N-terminal kinases in injury of hippocampus in rats exposed to chronic hypoxic hypercapnia

作　　者：李勇[1] 邓小龙[1] 邵胜敏[1] 陈松芳[1] 柯将琼[1] 王小同[1] 郑国庆[1] 

机构地区：[1]温州医学院第二附属医院神经内科,浙江温州325027

出　　处：《中国病理生理杂志》2009年第5期914-918,共5页Chinese Journal of Pathophysiology

基　　金：浙江省自然科学基金资助项目(No.Y205233);温州市科技厅课题资助项目(No.Y2005A152)

摘　　要：目的:探讨c-Jun氨基末端激酶(JNK)在慢性低O2高CO2大鼠海马损伤中的作用。方法:采用慢性低O2高CO2肺动脉高压大鼠模型。30只SD大鼠随机分为正常对照(NC)组、低O2高CO22周(2WH)组和低O2高CO24周(4WH)组,每组10只。Morris水迷宫检测行为学,用半定量逆转录-聚合酶链反应(RT-PCR)动态观察海马p-JNKmRNA的转录情况,免疫组织化学法测定p-JNK在海马CA1/CA3区的变化,TUNEL法检测海马CA1/CA3区神经细胞凋亡。结果:与NC组相比,低O2高CO22WH、4WH组大鼠寻找站台的平均逃避潜伏期延长、游泳总距离增加(P<0.01或P<0.05),且4WH组比2WH组潜伏期延长及游泳总距离增加更加明显(P<0.05);NC组大鼠海马仅见少量JNKmRNA及蛋白表达,低O2高CO2各组较NC组JNK表达明显增加(P<0.01或P<0.05),且4WH组比2WH组增加更明显(P<0.05)。低O2高CO22WH、4WH组的TUNEL阳性细胞数均明显多于NC组(P<0.01或P<0.05),且4WH组比2WH组增多明显(P<0.01)。结论:低O2高CO2能导致大鼠学习记忆障碍,可能与激活海马神经细胞内JNK有关。AIM ： To study the role of c - Jun N - terminal kinases （JNK） in injury of hippocampus in rats exposed to chronic hypoxic hypercapnia. METHODS： The pulmonary hypertension rat model was reproduced by chronic hypoxic hypercapnia exposure. Thirty rats were randomly divided into three groups （ 10 rats in each group） ： normal control （NC） group, hypoxic hyporcapnia 2 -week （2WH） and 4 -week （4WH） group. Morris water maze was used to examine the behavioral deficit. Semiquantitative reverse transcription -polymerase chain reaction was performed to observe the dy namic expression of JNK mRNA in the hippocampus of rats. The activity of p - JNK was detected by using SP immunochemical technique in hippocampus CA1/3, the number of apoptosis neurons was counted by TUNEL method. RFSULTS： Compared with NC group, rats in hypoxic hypercapnia 2WH and 4WH group displayed significant impairment in their performance assessed by two measures ： mean escape latencies and swim path distances （ P 〈 0. 05 or P 〈 0. 01 ）. The extent of impairment showed in exposure time - dependent manner. The expressions of p - JNK mRNA and protein were markedly higher in 2W and 4W group compared with NC group with the time of exposure extend （P 〈0. 01 or P 〈0. 05）, and more evident in 4WH group than 2WH （ P 〈 0. 05 ）. Apoptotic cells in hippocampus CA1/3 were occasionally found in NC group, and began to increase in chronic hypoxic hypercapnia rats with the time of exposure, which were higher than those in NC group （P 〈 0. 01 ）, and more apoptotic cells in 4WH group than 2WH group （ P 〈 0. 01 ） were observed. CONCLUSION ： The disorder of learning and memory in rats exposed to chronic hypoxic hypercapnia may be associated with the JNK activation in hippocampus.

关 键 词：低氧 高碳酸血 c—Jun氨基末端激酶 学习 记忆 细胞凋亡 海马 

分 类 号：R364.4[医药卫生—病理学] R743[医药卫生—基础医学]