Effect of Cross Electro-nape-acupuncture on cAMP-PKA Pathway in Medullary Tissue of Cerebral Hemorrhage Bulbar Injury Model Guinea Pigs

JIA Kunping; LIANG Qun; LIU Guanping; CAI Guofeng; WU Jianli

doi:10.13288/j.11-2166/r.2023.11.014

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Effect of Cross Electro-nape-acupuncture on cAMP-PKA Pathway in Medullary Tissue of Cerebral Hemorrhage Bulbar Injury Model Guinea Pigs

更新时间：2023-06-05

- Effect of Cross Electro-nape-acupuncture on cAMP-PKA Pathway in Medullary Tissue of Cerebral Hemorrhage Bulbar Injury Model Guinea Pigs
- Journal of Traditional Chinese Medicine Vol. 64, Issue 11, Pages: 1157-1164(2023)
- 作者机构：
  
  1.黑龙江中医药大学，黑龙江省哈尔滨市香坊区和平路24号，150040
  2.黑龙江中医药大学附属第二医院哈南分院
  3.黑龙江中医药大学附属第一医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2023.11.014
  CLC：
- Received：08 October 2022，
  
  Revised：2023-01-23，
  
  Published：02 June 2023
- 稿件说明：
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贾坤平,梁群,刘关平等.交叉电项针对脑出血延髓损伤模型豚鼠延髓组织cAMP-PKA通路的影响[J].中医杂志,2023,64(11):1157-1164.

JIA Kunping,LIANG Qun,LIU Guanping,et al.Effect of Cross Electro-nape-acupuncture on cAMP-PKA Pathway in Medullary Tissue of Cerebral Hemorrhage Bulbar Injury Model Guinea Pigs[J].Journal of Traditional Chinese Medicine,2023,64(11):1157-1164.
贾坤平,梁群,刘关平等.交叉电项针对脑出血延髓损伤模型豚鼠延髓组织cAMP-PKA通路的影响[J].中医杂志,2023,64(11):1157-1164. DOI： 10.13288/j.11-2166/r.2023.11.014.

JIA Kunping,LIANG Qun,LIU Guanping,et al.Effect of Cross Electro-nape-acupuncture on cAMP-PKA Pathway in Medullary Tissue of Cerebral Hemorrhage Bulbar Injury Model Guinea Pigs[J].Journal of Traditional Chinese Medicine,2023,64(11):1157-1164. DOI： 10.13288/j.11-2166/r.2023.11.014.

摘要

目的

探讨交叉电项针对脑出血延髓损伤豚鼠神经功能的影响及可能作用机制。

方法

240只豚鼠随机分为空白组、模型组、针刺组、交叉电项针组和电项针组，每组又分为干预1、3、7、14天4个时间点，每个时间点各12只。除空白组外，其余各组豚鼠采用自体血注入法制备脑出血延髓损伤模型。造模12 h后开始干预，针刺组豚鼠选取双侧“风池”“翳风”针刺，每次20 min，每日1次。交叉电项针组豚鼠以电针仪电极在项部交叉连接双侧“风池”“翳风”，电项针组豚鼠电针电极不交叉连接双侧“风池”“翳风”，均每次20 min，每日1次。空白组、模型组豚鼠给予同样的抓取固定，但不干预。分别于干预1、3、7、14天采用改良神经功能缺损量表（mNSS）评定豚鼠神经功能缺损程度；各时间点取豚鼠延髓组织免疫组织化学法检测突触生长相关蛋白43（GAP-43）、突触素（SYN）阳性表达，ELISA法检测环磷酸腺苷（cAMP）、蛋白激酶A（PKA）含量，Western blot法检测cAMP蛋白及磷酸化环磷酸腺苷反应元件结合蛋白（p-CREB）表达。

结果

空白组豚鼠无神经损伤。与空白组同时间比较，其余各组豚鼠在各时间点mNSS评分均显著增加（

＜0.01）；与模型组同时间比较，针刺组、电项针组和交叉电项针组豚鼠在干预3、7、14 天 mNSS评分均有不同程度降低（

＜0.01），各干预组间各时间点比较差异无统计学意义（

＞0.05）。与空白组同时间比较，模型组豚鼠延髓组织各时间点GAP-43阳性表达升高，SYN阳性表达降低，cAMP、PKA含量及cAMP、p-CREB蛋白表达均降低（

＜0.05或

＜0.01）。与模型组同时间比较，各干预组在干预3、7、14天GAP-43、SYN阳性表达，cAMP、PKA含量及cAMP、p-CREB蛋白表达均升高（

＜0.05或

＜0.01），且交叉电项针组在干预7、14天时各指标改善优于针刺组和电项针组（

＜0.05或

＜0.01）。

结论

交叉电项针可改善脑卒中延髓损伤豚鼠神经功能缺损情况，其机制可能与激活延髓组织cAMP-PKA通路从而改善延髓突触可塑性有关。

Abstract

Objective

To observe the effect and possible mechanism of cross electro-nape-acupuncture （CENA） on neurological function of guinea pigs with cerebral hemorrhage bulbar injury.

Methods

A total of 240 guinea pigs were randomly divided into blank group， model group， acupuncture group， CENA group and electro-nape-acupuncture （ENA） group， and each group was further divided into 1-， 3-， 7- and 14-day intervention timepoints， with 12 guinea pigs at each timepoint. The model of cerebral hemorrhage bulbar injury was established by injection of the guinea pigs' autologous blood in all the groups except for the blank group. Twelve hours after modelling， the guinea pigs in the acupuncture group were needled at bilateral “Fengchi （GB 20）” and “Yifeng

（SJ 17）”， 20 minutes each time， once a day. In CENA group， the positive pole of the needle was connected to “Fengchi （GB 20）”， while the negative pole was connected to the opposite side of “Yifeng （SJ 17）”； in ENA group， the positive pole of the needle was connected to “Fengchi （GB 20）”， while the negative pole was connected to “Yifeng （SJ 17）” on the same side； the intervention was applied 20 minutes each time， once a day. The guinea pigs in the blank group and the model group were given the same grabbing and fixation without intervention. After 1-， 3-， 7- and 14-day intervention， the neurologic function was assessed by using modified neurological severity scale （mNSS）. Positive expression of synapse growth-associated protein 43 （GAP-43） and synaptophysin （SYN） in guinea pig medullary tissue were detected by immunohistochemistry at each timepoint. Contents of cyclic adenosine monophosphate （cAMP） and protein kinase A （PKA） were detected by ELISA. The protein expressions of cAMP and phosphorylated cyclic AMP reponse response element binding protein （p-CREB） were detected by Western blot.

Results

The guinea pigs in the blank group had no neurological deficit. Compared to those in the blank group， the mNSS score at different timepoints in the other groups significantly increased （

＜0.01）. The mNSS score showed different degrees of reduction after 3-， 7- and 14-day intervention in the acupuncture， ENA and CENA groups compared to those measured at the same timepoints in the model group （

＜0.01）. There was no signi-ficant difference among acupuncture， ENA and CENA groups in mNSS score （

＞0.05）. Compared to the blank group， the model group had increased positive expression of GAP-43， decreased positive expression of SYN， reduced cAMP， PKA content and p-CREB protein expression in the medullary tissue at each timepoint （

＜0.05 or

＜0.01）. Compared to those in the model group measured at the same timepoint， the positive expression of GAP-43 and SYN， the cAMP and PKA content， and the protein expression of cAMP and p-CREB in the acupuncture， CENA and ENA groups after 3-， 7- and 14-day intervention significantly increased （

＜0.05 or

＜0.01）， and the CENA group showed more significant improvements than the acupuncture group and ENA group in all above mentioned outcomes measured after 7- and 14-day intervention （

＜0.05 or

＜0.01）.

Conclusion

CENA can improve the neurological deficit in the guinea pigs with medullary injury after stroke， which is likely related to the activation of the cAMP-PKA pathway in the medullary tissue to improve the synaptic plasticity of the medulla.

关键词

Keywords

references

王陇德，彭斌，张鸿祺，等 . 《中国脑卒中防治报告2020》概要［J］. 中国脑血管病杂志， 2022 ， 19 （ 2 ）： 136 - 144 .

李傲，朱素英，陈梦飞，等 . 高血压脑出血患者流行病学及临床特征分析［J］. 中华脑科疾病与康复杂志（电子版）， 2018 ， 8 （ 1 ）： 11 - 14 .

焦敏娜 . 交叉电项针治疗中风后假性延髓麻痹的临床观察［D］. 哈尔滨：黑龙江中医药大学， 2020 .

彭艳霞，唐明，陈天龙，等 . 交叉电项针结合吞咽训练对脑卒中后气管切开患者吞咽功能及肺部感染的影响［J］. 广州中医药大学学报， 2022 ， 39 （ 1 ）： 83 - 87 .

贾坤平，王秀珍，吴建丽，等 . “交叉电项针”治疗重症脑出血后气管切开临床观察［J］. 上海针灸杂志， 2020 ， 39 （ 3 ）： 300 - 304 .

裴思颖，蔡国锋，刘凯，等 . 交叉电项针对脑出血合并机械通气患者撤机的影响［J］. 中国中医急症， 2021 ， 30 （ 11 ）： 1944 - 1946 .

CAI G ， ZHUANG Z ， JIA K ， et al . Effects of cross electro-nape-acupuncture （CENA） on recover of consciousness and tracheotomy tube sealing in serious cerebral hemorrhage ［J］. Am J Transl Res ， 2022 ， 14 （ 3 ）： 1868 - 1876 .

TAO C ， ZHANG R ， HU X ， et al . A novel brainstem hemorrhage model by autologous blood infusion in rat： white matter injury， magnetic resonance imaging， and neurobehavioral features ［J］. J Stroke Cerebrovasc Dis ， 2016 ， 25 （ 5 ）： 1102 - 1109 .

GAO F ， YANG S ， WANG J ， et al . cAMP-PKA cascade： an outdated topic for depression？［J］. Biomed Pharmacother ， 2022 ， 150 ： 113030 . doi： 10.1016/j.biopha. 2022. 113030 http://dx.doi.org/10.1016/j.biopha.2022.113030 .

诸葛启钏 . 豚鼠脑立体定位图谱［M］. 北京：人民卫生出版社， 2005 ： 47 .

LONGA EZ ， WEINSTEIN PR ， CARLSON S ， et al . Reversible middle cerebral artery occlusion without craniectomy in rats ［J］. Stroke ， 1989 ， 20 （ 1 ）： 84 - 91 .

李辞蓉，华兴邦，周浩良，等 . 豚鼠针灸穴位图谱的研制［J］. 上海针灸杂志， 1992 （ 2 ）： 28 - 30 .

CHEN J ， LI Y ， WANG L ， et al . Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats ［J］. Stroke ， 2001 ， 32 （ 4 ）： 1005 - 1011 .

姜泽飞，贾宏彬，岳广晴，等 . 针刺治疗假性延髓麻痹吞咽障碍的取穴规律研究［J］. 中国针灸， 2022 ， 42 （ 4 ）： 465 - 470 .

CAI GF ， SUN ZR ， ZHUANG Z ， et al . Cross electro-nape-acupuncture ameliorates cerebral hemorrhage-induced brain damage by inhibiting necroptosis ［J］. World J Clin Cases ， 2020 ， 8 （ 10 ）： 1848 - 1858 .

MERINO P ， DIAZ A ， TORRE ER ， et al . Urokinase-type plasminogen activator （uPA） regulates the expression and function of the growth- associated protein-43 （GAP-43） in the synapse ［J］. J Biol Chem ， 2019 ， 295 （ 2 ）： 619 - 630 .

魏玉婷，朱田田，贾静，等 . 针灸干预阿尔茨海默病的作用机制研究进展［J］. 针刺研究， 2022 ， 47 （ 4 ）： 362 - 368 .

CRESTINI A ， PISCOPO P ， CAMPEGGI LM ， et al . Proteic marker of hypoxic-ischemic damage ［J］. Ann Ist Super Sanita ， 2001 ， 37 （ 4 ）： 581 - 591 .

ZAK N ， MOBERGET T ， BØEN E ， et al . Longitudinal and cross-sectional investigations of long-term potentiation-like cortical plasticity in bipolar disorder type Ⅱ and healthy individuals ［J］. Transl Psychiatry ， 2018 ， 8 （ 1 ）： 103 .

HWANG YS ， OH SW ， PARK SH ， et al . Melanogenic effects of maclurin are mediated through the activation of cAMP/PKA/CREB and p38 MAPK/CREB signaling pathways ［J］. Oxid Med Cell Longev ， 2019 ， 2019 ： 9827519 . doi： 10.1155/2019/9827519 http://dx.doi.org/10.1155/2019/9827519 .

MASSENGILL CI ， DAY-COONEY J ， MAO T ， et al . Genetically encoded sensors towards imaging cAMP and PKA activity in vivo ［J］. J Neurosci Methods ， 2021 ， 362 ： 109298 . doi： 10.1016/j.jneumeth.2021.109298 http://dx.doi.org/10.1016/j.jneumeth.2021.109298 .

JIANG HL ， ZHANG XH ， WANG Y ， et al . Mechanisms underlying the antidepressant response of acupuncture via PKA/CREB signaling pathway ［J］. Neural Plast ， 2017 ， 2017 ： 4135164 . doi： 10.1155/2017/4135164 http://dx.doi.org/10.1155/2017/4135164 .

LIN R ， LI X ， LIU W ， et al . Electro-acupuncture ameliorates cognitive impairment via improvement of brain-derived neurotropic factor-mediated hippocampal synaptic plasticity in cerebral ischemia-reperfusion injured rats ［J］. Expe Ther Med ， 2017 ， 14 （ 3 ）： 2373 - 2379 .

吕靖 . cAMP/PKA/CREB信号通路在缺氧预处理逆转丙泊酚致发育期豚鼠海马神经元毒性中的作用［D］. 南宁：广西医科大学， 2018 .

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