尼莫地平对惊厥持续状态幼鼠海马葡萄糖调节蛋白78、p38丝裂素激活蛋白激酶表达的影响  

Expressions of glucose - regulated protein 78 and p38 mitogen - activated protein kinase signal pathway in the hippocampus of status convulsion rat and the effect of Nimodipine

作　　者：徐敏慧[1] 赵艳民[2] 楼菁菁 周朱瑛[3] 王海萍[3] 李光乾[3] 

机构地区：[1]金华市中心医院儿科(浙江大学金华医院),321000 [2]金华职业技术学院医学院外科 [3]浙江中医药大学附属儿童医院儿科

出　　处：《中华实用儿科临床杂志》2015年第5期384-388,共5页Chinese Journal of Applied Clinical Pediatrics

基　　金：金华市科技计划项目（2011-3-023）

摘　　要：目的 探讨葡萄糖调节蛋白78（GRP78）、p38丝裂素激活蛋白激酶（p38MAPK）相关信号通路在惊厥性脑损伤中的作用及尼莫地平对其的影响。方法 雄性SD 幼年大鼠分为惊厥持续状态组（SC组）、尼莫地平组（NM 组）、正常对照组（NC组）。采用免疫组织化学法、反转录（RT）-PCR技术检测海马CA1区GRP78/Bip、p38MAPK蛋白、mRNA表达动态变化；采用原位末端标记（TUNEL）检测神经细胞的凋亡。结果 1.免疫组织化学：GRP78/Bip蛋白惊厥后4 h开始增加，24 h达高峰，之后下降。p38MAPK 蛋白惊厥后4 h表达开始增加，24 h达高峰，48 h稍有下降。2.RT-PCR：SC组海马 GRP78/Bip mRNA 表达于惊厥后4 h开始少量增加，24 h达高峰，48h回到基线水平。NM 组4h，24h和48h表达情况较SC组和NC组均明显升高（P均〈0.05）。SC组p38MAPK mRNA于惊厥后4h开始表达，24h达高峰，48h后有所下降，但均高于NC组；NM 组24h时间点明显高于NC组（P 〈0.01）。3.TUNEL：SC组海马CA1区TUNEL阳性细胞于惊厥后4 h已有少量表达，48 h达高峰，之后有下降趋势；且24 h、48 h2个时间点均明显高于 NC组（P均 〈0.05）。NM 组24 h、48 h时间点TUNEL阳性细胞表达水平较SC组明显降低（P均〈0.05）；但仍高于NC组（P 〈0.01）。结论 GRP78信号通路可能通过激活p38MAPK介导细胞凋亡，尼莫地平预处理可影响GRP78/Bip和 p38MAPK 的表达，缓解内质网应激，减轻惊厥后海马病理损伤程度。Objective To explore the role of glucose - regulated protein 78 （ GRP78 ）, p38 mitogen - activated protein kiuase（p38MAPK） signal pathway in seizure -reduced brain injures and the regulatory effect of Nimodipine on it. Methods Sprague -Dawley（SD） rats were randomly divided into status convulsion group （SC group） , Nimodipine group（ NM group） , and a normal control group（ NC group）. The expressions of GRP78/Bip and p38MAPK mRNA and protein were detected by reverse transcription（RT） -PCR and immunohistochemistry. The expression of apoptosis cells was observed by TdT - mediated dUTP nick end labeling （TUNEL）. Results （ 1 ） Immuuohistochemistry ： at 4 h after induction of status convulsion, the expression of GRP78 protein in the hippocampus CA1 domain began increasing slightly,and reached a maximum at 24 h,and then began decreasing slowly;at 4 h after induction of status convulsion, the expression of p38MAPK protein in the hippocampus CA1 domain began increasing, and reached a maximum at 24 h, and decreased remarkably at 48 h. （ 2 ） RT - PCR ： at 4 h after induction of status convulsion, the expression of GRP78 protein in the hippocampus CA1 domain began increasing slightly, and reached a maximum at 24 h,and then began de- creasing slowly. The NM group was much higher than the SC group and the NC group （ all P 〈 0.05 ） ; at 4 h after induc- tion of status convulsion,the expression of p38MAPK protein in the hippoeampus CA1 domain began increasing, and reached a maximum at 24 h, and decreased remarkably at 48 h ; the NM group was much lower than the SC group, and higher than the NC group（ all P 〈 0.05）. （3） TUNEL： at 4 h after induction of status convulsion, the expression of the TUNEL positive cells in the hippocampus CA1 domain began increasing slightly,and reached a maximum at 48 h, and then began decreasing, and there was no difference between SC group and NC group;the NM group was much lower than the SC group（ all P 〈 0.05 ）. Conclusions The corre

关 键 词：惊厥持续状态 葡萄糖调节蛋白78 p38丝裂素激活蛋白激酶 

分 类 号：R720.597[医药卫生—急诊医学]