PTEN、Akt与CREB基因在偏头痛大鼠三叉神经节的表达  

Expression of phosphatase and tensin,serine-threonine kinase,and cAMP response element-binging protein in trigeminal ganglia of rats with migraine

作　　者：桂蓓[1] 张聪[2] 申崇标[1] 陈力学[1] 秦光成[1] 周冀英[1] 谭戈[1] 

机构地区：[1]重庆医科大学附属第一医院实验研究中心,重庆市神经病学重点实验室,重庆400016 [2]第三军医大学实验动物中心,重庆400038

出　　处：《第三军医大学学报》2010年第11期1169-1172,共4页Journal of Third Military Medical University

基　　金：重庆市自然科学基金(CSTC2007BB5287);重庆医科大学附一院医学科学基金(YXJJ2009-15)~~

摘　　要：目的检测第10号染色体同源丢失性磷酸酶张力蛋白基因(phosphatase and tensin homolog deleted on chro-mosome ten,PTEN)、丝氨酸/苏氨酸蛋白激酶(serine-threonine kinase,Akt)与cAMP反应元件结合蛋白(cAMP responseelement-binding protein,CREB)基因在偏头痛模型大鼠三叉神经节的表达情况,探讨其在偏头痛发病机制中的相互关系及作用。方法通过硝酸甘油(glyceryl trinitrate,GTN)法建立大鼠偏头痛模型,分别在GTN注射后1、4、12和24h,取三叉神经节通过RT-PCR和免疫组化法对PTEN、Akt和CREB基因在mRNA和蛋白水平进行检测。结果 PTEN的基因与蛋白表达开始呈下降趋势,至GTN12h时分别为(0.42±0.07)(0.19±0.02),较对照组(1.00±0.07)(0.36±0.02)有显著降低(P<0.05),但到24h时基因与蛋白表达量分别为(3.09±0.21)(0.45±0.05),又明显回升(P<0.05);Akt与PTEN呈相反变化趋势,基因与蛋白表达在GTN4h(1.38±0.07)(0.23±0.03)和12h(1.42±0.03)(0.25±0.02)时显著增加(P<0.05),24h(0.88±0.15)(0.15±0.06)表达又降至正常水平(P>0.05);而GTN各组的CREB的基因与蛋白表达均较对照组(1.00±0.07)(0.43±0.03)有显著降低(P<0.05),24h(0.42±0.14)(0.27±0.05)表达量降到最低(P<0.05)。PTEN与Akt、CREB的基因表达呈显著负相关,r分别为-0.671,-0.484(P<0.05),蛋白表达也呈显著负相关,r分别为-0.563,-0.430(P<0.05),而Akt与CREB的基因及蛋白表达相关性不显著,r分别为0.272,-0.041(P>0.05)。结论偏头痛大鼠三叉神经节中PTEN、Akt及CREB在GTN不同时间点表达发生改变,且PTEN调控了Akt与CREB的表达,可能通过影响神经突触可塑性,参与偏头痛的发生发展过程。Objective To detect the expression of phosphatase and tensin （ PTEN） ,serine-threonine kinase （ Akt） and cAMP response element-binding protein （ CREB） in trigeminal ganglia of rats with migraine and to study its role in pathogenesis of migraine. Methods A rat model of migraine was established using glyceryl trinitrate （ GTN）. Expression of PTEN,Akt,and CREB at mRNA and protein levels in trigeminal ganglia was detected by RT-PCR and immunohistochemistry 1,4,12 and 24 h respectively,after the model was established. Results The expression level of PTEN was 0. 42 ± 0. 07 and 0. 19 ± 0. 02 respectively at 12 h （ P 0. 05） ,and was 3. 09 ±0. 21 and 0. 45 ±0. 05 at 24 h in experimental group,which was higher than that （ 1. 00 ±0. 07 and 0. 36 ±0. 02） in control group （ P 0. 05）. The expression level of Akt was 1. 38 ±0. 07 and 0. 23 ± 0. 03,1. 42 ± 0. 03 and 0. 25 ± 0. 02 at 4 and 12 h,and was 0. 88 ± 0. 15 and 0. 15 ± 0. 063 at 24 h in experimental group,which was lower than that （ 1. 00 ± 0. 07 and 0. 43 ± 0. 03） in control group （ P 0. 05）. The expression level of CREB was significantly lower in experimental group than in control group （ P 0. 05） ,and was 0. 42 ± 0. 14 and 0. 27 ± 0. 05 （ the lowest） at 24 h （ P 0. 05）. The expression of PTEN was negatively correlated to Akt （ r = -0. 671 and -0. 563） and CREB （ r = -0. 484 and -0. 430 or r = 0. 272 and -0. 041） （ P 0. 05）. Conclusion Expression of PTEN,Akt and CREB in trigeminal ganglia of rats with migraine is changed at different time points. PTEN regulates the expression of Akt and CREB,therebyaffecting synaptic plasticity,and is thus involved in pathogenesis of migraine.

关 键 词：PTEN AKT CREB 偏头痛 三叉神经节 

分 类 号：R747.202[医药卫生—神经病学与精神病学] R322.81[医药卫生—临床医学]