[1]陈　伟,郑　平,任大斌,等.cAMP对大鼠颅脑损伤后神经功能及脑水肿的影响[J].中国临床神经外科杂志,2019,(04):226-229.[doi:10.13798/j.issn.1009-153X.2019.04.012]
　CHEN Wei,ZHENG Ping,REN Da-Bin,et al.Role of inhibition of phosphorylated Cx43 by PKA pathway in treatment for traumatic brain injury[J].,2019,(04):226-229.[doi:10.13798/j.issn.1009-153X.2019.04.012]
点击复制

cAMP对大鼠颅脑损伤后神经功能及脑水肿的影响()
分享到：

《中国临床神经外科杂志》[ISSN:1009-153X/CN:42-1603/TN]

卷:
期数:
2019年04期
页码:
226-229
栏目:
论著
出版日期:
2019-04-27

文章信息/Info

Title:
Role of inhibition of phosphorylated Cx43 by PKA pathway in treatment for traumatic brain injury
文章编号:
1009-153X（2019）04-0226-04
作者:
陈　伟; 郑　平; 任大斌; 童武松; 刘　宁; 赵　麟
330008 南昌，南昌大学第一附属医院神经外科（陈　伟）201299 上海，上海健康医学院附属上海浦东新区人民医院神经外科（郑　平、任大斌、童武松）；210009 南京，南京医科大学第一附属医院神经外科（刘　宁、赵　麟）
Author(s):
CHEN Wei1;  ZHENG Ping2;  REN Da-Bin2;  TONG Wu-Song2;  LIU Ning3;  ZHAO Lin3.
1. Department of Neurosurgery, The First Affliated Hospital, Nanchang University, Nanchang 330008, China; 2. Department of Neurosurgery, The People's Hospital of Shanghai Pudong New Area, Shanghai University of Medicine and Health Sciences, Shanghai 201299, China; 3. Department of Neurosurgery, The First Affliated Hospital, Nanjing Medical University, Nanjing, 210009, China
关键词:
颅脑损伤; 脑水肿; 缝隙连接蛋白43; 谷氨酸转运蛋白-1; 钠钾ATP酶; 大鼠
Keywords:
Traumatic brain injury;  Cx43;  GLT-1;  Na-K-ATP;  Glutamate;  Expression;  Roles
分类号:
R 651.1+5
DOI:
10.13798/j.issn.1009-153X.2019.04.012
文献标志码:
A
摘要:
目的 探讨蛋白激酶A（PKA）激活物cAMP对颅脑损伤（TBI）大鼠神经功能、脑水肿的影响。方法 选取120只成年雄性SD大鼠随机分为6组（每组20只）：假手术组（暴露硬脑膜而不给予液压打击）；高、中、低剂量cAMP组（TBI后1 h腹腔注射60、40、20 mg/kg PKA激活物8-Bromo-cAMP）；溶媒组（TBI后1 h腹腔注射cAMP溶媒二甲基亚砜10 μl）；模型组（液压打击处理）。TBI后48 h，采用神经损伤严重程度评分（NSS）评估神经功能，干湿重法测定脑含水量，免疫印迹法检查海马细胞外信号调节激酶1/2（ERK1/2）、非磷酸化缝隙连接蛋白43（NP-Cx43）、谷氨酸转运蛋白-1（GLT-1）及钠钾ATP酶的表达，高效液相色谱法检测海马谷氨酸（Glu）的含量。结果 TBI后，大鼠NSS明显增高（P<0.05），脑含水量明显增加（P<0.05），海马ERK1/2表达水平明显增加（P<0.05），海马Glu含量明显增加（P<0.05），而NP-Cx43、GLT-1、钠钾ATP酶表达水平明显降低（P<0.05）；cAMP干预后，显著逆转这些反应（P<0.05），而且呈剂量依赖性。结论 大鼠TBI后，给予cAMP干预，激活PKA，可通过门卫效应抑制ERK1/2，使NP-Cx43、GLT-1及钠钾ATP酶水平明显增高，进一步降低Glu等脑毒性代谢产物、缓解脑水肿，从而改善大鼠神经功能。
Abstract:
Objective To investigate the effect of inhibition of phosphorylated connexin (Cx)43 by protein kinase A (PKA) on the treatment of traumatic brain injury (TBI). Methods One hundred and twenty rats were randomly divided into 6 groups of 20 animal each, i.e. sham operation group, treatment groups, 1, 2 and 3 in which the rats received peritoneal injection of 20, 40 and 60 mg/kg 8-Bromo-cAMP respectively 1 hour after TBI, vehicle group in which the rats received peritoneal injection of dimethyl sulphoxide 1 hour after TBI and TBI group in which the rats underwent TBI only and did not receive any treatment. TBI models were established with fluid percussion device in the rats. Ten rates were sacrificed 48 hours after TBI and their brain water content was determined after the behavioral disordes were determined by Neurological Severity score (NSS) in all the groups. Another 10 rates were sacrificed 48 hours after TBI and their hippocampal astorcytes were obtained in order to determine the expressions of extracellular regulated protein kinase (ERK)1/2, nonphorylated (NP)-Cx43, glutamic transducin (GLT)-1 and Na-K-ATP determined by western blot and glutamic acid (Glu) by high pressure liquid chromatography. Result The levels of NP-Cx43, GLT-1 and Na-K-ATP expressions were significantly higher in all the treatment groups and sham operation group than those in other two groups (P<0.05). The levels of ERK1/2 and Glu expressions, brain water content and the scores of NSS were significantly lower in all the treatment groups and sham operation operation group than those in the TBI and vehicle groups (P<0.05). These changes were 8-Bromo-cAMP dose-dependent. Conclusions Activation of PKA pathway can inhibit ERK1/2 pathway, and up-regulate the levels of NP-Cx43, GLT-1 and Na-K-ATP protein expressions in the hippocampal astrocytes, which can reduce the contents of brain water and Glu on the brain in the rate with TBI.

参考文献/References:

[1] Chen W, Feng JG, Tong WS. Phosphorylation of astrocytic connexin43 by ERK1/2 impairs blood-brain barrier in acute cerebral ischemia [J]. Cell Biosci, 2017, 7: 43.
[2] Dukic AR, Gerbaud P, Pidoux G, et al. Ezrin-anchored PKA phophorylates serine 369 and 373 on Cx43to enhance gap junction assembly, commuication and cell fusion [J]. Biochem J, 2018, 475(2): 455-476.
[3] Pidoux G, Tasken K. Anchored PKA as a gatekeeper for gap junctions [J]. Commun Inter Biol, 2015, 8(4): e1057361.
[4] Glenn TC, Hirt D, Martin NA, et al. Metabolomic analysis of CSF from patients with severe TBI [J]. Acta Neurochir Suppl, 2013, 118: 115-119.
[5] Seitelberger F, Lassmann H, Hornykiewicz D. Some mecha- nism of brain edema studied in a kainic acid model [J]. Acta Neurobiol Exp, 1990, 50(4-5): 263-267.
[6] Elfgang C, Eckert R, Willecke K, et al. Specific permeabi- lity and selective formation of gap junction channels in connexin-tranfected Hela cells [J]. J. Cell Biol, 129, 805- 817.
[7] De Bock M, C μlot M, Simon AM, et al. Connexins channels provide a target to manip μlate brain endothelial calcium dynamic and blood-brain barrier permeability [J]. J Cere Blood Flow Metab, 2011, 31(9): 1942-1957.
[8] Avila MA, Boone DR, DeWitt DS, et al. Cerebrovascular connexin expression: effects of traumatic brain injury [J]. J Neurotrauma, 2011, 28(9): 1803-1811.
[9] Chen B, Sun L, Ma J，et al. Correlation between connexin and traumatic brain injury in patients [J]. Brain Behav, 2017, 7: e00770.
[10] Langer J, Theis M, Rose CR, et al. Gap junction mediate intercell μlar spread of sodium between hippocampal astrocytes in situ [J]. Glia, 2012, 60(2): 239-252.
[11] Figiel M, Allritz C, Engele J, et al. Gap junction control of glial glumate transport expression [J]. Mol Cell Neurosci, 2007, 35(1): 130-137.
[12] Viczenzova C, Szeiffova Bacova B, Tribulova N, et al. Myo- cardial Cx43 and PKC singalling are involved in adapation of the heart to irradiation induced injury: Implication of miR-1 and miR-21 [J]. Gen Physiol Biophys, 2016, 35(2): 215-222.
[13] Guillaume P, Pascale G, Jim D, et al. A PKA-erzin-Cx43 signaling complex controls gap junction communcation and thereby trophoblast cell fusion [J]. J Cell Sci, 2014, 127: 4172-4185.
[14] Pidoux G, Tasken K. Anchored PKA as gatekeeper for gap junction [J]. Commun Integr Biol, 2015, 8(4): e1057361.
[15] Solan JL, Marquez L, Lamper PD, et al. Phosphorylation at S365 is gatekeeper event that changes structure of Connexin 43 and prevents down reg μlation by PKC [J]. J Cell Biol, 2007, 179(6): 1301-1309.

相似文献/References:

[1]张善纲 综述.现代战争中颅脑损伤的特点及功能康复[J].中国临床神经外科杂志,2015,(11):701.[doi:10.13798/j.issn.1009-153X.2015.11.021]
[2]钟秀均　黄书岚.复方醒脑液治疗颅脑损伤后综合征的临床观察[J].中国临床神经外科杂志,2016,(05):278.[doi:10.13798/j.issn.1009-153X.2016.05.007]
　ZHONG Xiu-jun,HUANG Shu-lan..Clinical observation on treatment of compound decoction for cerebral prorection for post-traumatic brain syndrome[J].,2016,(04):278.[doi:10.13798/j.issn.1009-153X.2016.05.007]
[3]李国亮　邸　方　杨亚东.香芹酚通过抑制脑水肿与氧化应激反应保护大鼠 颅脑损伤[J].中国临床神经外科杂志,2016,(05):283.[doi:10.13798/j.issn.1009-153X.2016.05.009]
　LI Guo-liang,DI Fang,YANG Ya-dong..Carvacrol protects against traumatic brain injury in rats through suppressing the brain edma and oxidative stress[J].,2016,(04):283.[doi:10.13798/j.issn.1009-153X.2016.05.009]
[4]罗心凯　陈治标　陈谦学.免缝胶原海绵人工硬脑膜在颅脑损伤大骨瓣减压术中的应用[J].中国临床神经外科杂志,2016,(06):357.[doi:10.13798/j.issn.1009-153X.2016.06.012]
　LUO Xin-kai,CHEN Zhi-biao,CHEN Qian-xue..Application of collagen sponge artificial dura without suturing to big bone flap decompression after traumatic brain injury[J].,2016,(04):357.[doi:10.13798/j.issn.1009-153X.2016.06.012]
[5]贺瑛福　肖宗宇　马进海　许常林　裴　杰　袁　岗　张广华　 巨　虎.高海拔地区重型颅脑损伤血清FSH、LH、PRL的变化[J].中国临床神经外科杂志,2016,(06):359.[doi:10.13798/j.issn.1009-153X.2016.06.013]
　HE Ying-fu,XIAO Zong-yu,MA Jin-hai,et al.Changes in serum FSH, LH and PRL levels in the patients with severe traumatic brain injury in plateau[J].,2016,(04):359.[doi:10.13798/j.issn.1009-153X.2016.06.013]
[6]满明昊　李立宏　杨彦龙　李　敏　郭少春.颅脑损伤术后细胞免疫指标变化及脾多肽对其影响[J].中国临床神经外科杂志,2016,(06):362.[doi:10.13798/j.issn.1009-153X.2016.06.014]
　MAN Ming-hao,LI Li-hong,YANG Yan-yong,et al.Changes in peripheral cells immunity after operation and effect of spleen polypeptide on them in patients with traumatic brain injury[J].,2016,(04):362.[doi:10.13798/j.issn.1009-153X.2016.06.014]
[7]程　勇　秦加新　戢翰升　李　刚　聂劲林　李　强.颅脑损伤术中急性脑膨出的相关因素分析[J].中国临床神经外科杂志,2016,(06):374.[doi:10.13798/j.issn.1009-153X.2016.06.019]
[8]张一帆 综述　张国来 审校.弥漫性轴索损伤影像学诊断的研究进展[J].中国临床神经外科杂志,2016,(07):442.[doi:10.13798/j.issn.1009-153X.2016.07.020]
[9]陈吉钢　张丹枫　魏嘉良　邹　伟　侯立军.创伤性眶上裂综合征的治疗陈吉钢[J].中国临床神经外科杂志,2016,(04):200.[doi:10.13798/j.issn.1009-153X.2016.04.003]
　CHEN Ji-gang,ZHANG Dan-feng,WEI Jiang-liang,et al.Management of traumatic superior orbital fissure syndrome (report of 22 cases)[J].,2016,(04):200.[doi:10.13798/j.issn.1009-153X.2016.04.003]
[10]肖连福　黄瑞宏　陈昌勇.外伤性颅内静脉窦血栓形成1例[J].中国临床神经外科杂志,2016,(04):256.[doi:10.13798/j.issn.1009-153X.2016.04.024]
[11]陈　进　徐绪卿　祝　斐　金卫星　路　遥.白蛋白联合呋塞米降低颅脑损伤患者颅内压的临床观察[J].中国临床神经外科杂志,2015,(12):757.[doi:10.13798/j.issn.1009-153X.2015.12.019]

备注/Memo

备注/Memo:
（2019-01-15收稿， 2019-02-18修回） 基金项目：国家自然科学基金（81701231）；上海市自然科学基金（16ZR1431500）；上海市浦东新区科委民生项目（PKJ2016-Y31）；上海健康医学院种子基金（SFP-18-21-13-007；SFP-18-21-13-005） 通讯作者：赵　麟，E-mail：zl_nirvana@126.com
更新日期/Last Update: 2019-04-27