[1]王岩英,周进国,刘晓宁,等.基于环磷酸腺苷/蛋白激酶A/环磷酸腺苷反应元件结合蛋白通路探究丙泊酚对局灶性脑缺血再灌注大鼠神经功能改善机制[J].陕西医学杂志,2024,(4):455-461.[doi:DOI:10.3969/j.issn.1000-7377.2024.04.005]
　WANG Yanying,ZHOU Jinguo,LIU Xiaoning,et al.Mechanism of propofol improving neurological function in rats with focal cerebral ischemia-reperfusion based on cAMP/PKA/CREB pathway[J].,2024,(4):455-461.[doi:DOI:10.3969/j.issn.1000-7377.2024.04.005]
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基于环磷酸腺苷/蛋白激酶A/环磷酸腺苷反应元件结合蛋白通路探究丙泊酚对局灶性脑缺血再灌注大鼠神经功能改善机制
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2024年4期
页码:
455-461
栏目:
基础研究
出版日期:
2024-04-05

文章信息/Info

Title:
Mechanism of propofol improving neurological function in rats with focal cerebral ischemia-reperfusion based on cAMP/PKA/CREB pathway
作者:
王岩英; 周进国; 刘晓宁; 王 芳; 张光信
(邯郸市第一医院麻醉科,河北 邯郸 056002)
Author(s):
WANG Yanying; ZHOU Jinguo; LIU Xiaoning; WANG Fang; ZHANG Guangxin
(Department of Anesthesiology,Handan First Hospital,Handan 056002,China)
关键词:
丙泊酚;  局灶性脑缺血再灌注损伤;  神经功能;  环磷腺苷;  蛋白激酶A;  环磷腺苷效应元件结合蛋白
Keywords:
Propofol;  Focal cerebral ischemia-reperfusion injury;  Neurological function;  Cyclic adenosine monophosphate;  Protein kinase A;  cAMP response element binding protein
分类号:
R -332
DOI:
DOI:10.3969/j.issn.1000-7377.2024.04.005
文献标志码:
A
摘要:
目的:基于环磷酸腺苷/蛋白激酶A/环磷酸腺苷反应元件结合蛋白(cAMP/PKA/CREB)通路探究丙泊酚对局灶性脑缺血再灌注大鼠神经功能的改善机制。方法:采用改良线栓法缺血2 h,再灌注24 h建立大鼠脑缺血再灌注损伤(CIRI)模型,将造模成功大鼠随机分为模型组和丙泊酚低(1 mg/ml)、中(2.5 mg/ml)、高剂量(5 mg/ml)组,各12只,另设含有12只大鼠的假手术组。分组后即开始给药,1次/d,共4周,末次给药12 h后,采用改良神经功能评分(mNSS)法进行神经缺损评分; 采用TTC染色法检测脑梗死面积; HE、Nissl染色进行神经元细胞及尼氏小体形态学观察; Tunel 法进行神经元细胞凋亡检测; Elisa法检测脑组织cAMP、脑源性神经营养因子(BDNF)、神经生长因子(NGF)含量; 免疫荧光法检测脑组织环磷酸腺苷(cAMP)、p-PKA、p-CREB阳性细胞数及其蛋白共表达阳性细胞数; Western blot法检测脑组织PKA、p-PKA、CREB、p-CREB蛋白表达量。结果:模型组大鼠比较假手术组大鼠的mNSS评分、脑梗死面积百分比显著增加(均P<0.05),HE染色和Nissl染色可见明显的神经元细胞损伤和尼氏小体破坏,脑组织cAMP、BDNF、NGF含量和PKA、p-PKA、CREB、p-CREB蛋白表达量显著下降,模型组大鼠比较假手术组大鼠的cAMP、p-PKA、p-CREB阳性细胞数和蛋白共表达阳性细胞数也明显下降(均P<0.05)。与模型组比较,丙泊酚给药组大鼠mNSS评分、脑梗死面积百分比显著降低(均P<0.05),HE染色和Nissl染色可见神经元细胞损伤和尼氏小体破坏有不同程度改善,脑组织cAMP、BDNF、NGF含量和PKA、p-PKA、CREB、p-CREB蛋白表达量显著升高(均P<0.05),cAMP、p-PKA、p-CREB阳性细胞数及其蛋白共表达阳性细胞数均显著升高(均P<0.05)。结论:丙泊酚可能通过cAMP/PKA/CREB通路改善CIRI大鼠神经功能。
Abstract:
Objective:To investigate the mechanism of propofol in improving neurological function in rats with focal cerebral ischemia-reperfusion based on the cAMP/protein kinase A/cAMP response element-binding protein(cAMP/PKA/CREB)pathway.Methods:The rats CIRI model was established by improved thread occlusion for 2 hours and reperfusion for 24 hours.The successful rats were randomly divided into model group,and low(1 mg/ml),medium(2.5 mg/ml)and high dose(5 mg/ml)propofol groups with 12 rats in each group,and 12 rats in sham operation group.After grouping,the drug was administered once a day for 4 weeks.After the last administration for 12 hours,the nerve defect was scored by mNSS method; TTC staining was used to detect the area of cerebral infarction; HE and Nissl staining were used to observe the morphology of neuronal cells and Nissl bodies; TUNEL method was used to detect neuronal apoptosis; the contents of cAMP,BDNF and NGF in brain tissue were detected by ELISA; the number of cAMP,p-PKA,p-CREB positive cells and the number of protein co-expression positive cells were detected by immunofluorescence; the protein expressions of PKA,p-PKA,CREB and p-CREB were detected by Western blot.Results:Compared with the sham group,the mNSS scores,percentage of cerebral infarction area in model group increased significantly(all P<0.05).HE staining and Nissl staining showed obvious neuronal cell damage and Nissl body destruction.The contents of cAMP,BDNF,NGF and the expression of PKA,p-PKA,CREB and p-CREB protein in brain tissue decreased significantly,and the number of cAMP,p-PKA,p-CREB positive cells and their protein co-expression positive cells decreased significantly(all P<0.05).Compared with the model group,the mNSS scores and the percentage of cerebral infarction area in the propofol administration group were significantly lower(all P<0.05).HE staining and Nissl staining showed that the neuronal cell damage and Nissl body destruction were improved in varying degrees,and the contents of cAMP,BDNF,NGF and the expression of PKA,p-PKA,CREB and p-CREB proteins in brain tissue were significantly higher,the number of cAMP,p-PKA,p-CREB positive cells and their protein co-expression positive cells increased significantly(all P<0.05).Conclusion:Propofol may improve the neurological function of CIRI rats through cAMP/PKA/CREB pathway.

参考文献/References:

[1] WU M Y,YIANG G T,LIAO W T,et al.Current mechanistic concepts in ischemia and reperfusion injury[J].Cellular Physiology & Biochemistry International Journal of Experimental Cellular Physiology Biochemistry & Pharmacology,2018,46(4):1650-1667.
[2] LIANG Z,ZHANG W,ZHU T,et al.Ischemia-reperfusion injury in peripheral artery disease and traditional chinese medicine treatment[J].Evidence-Based Complementary and Alternative Medicine,2021:4954070.
[3] GONG L,TANG Y,AN R,et al.RTN1-C mediates cerebral ischemia/reperfusion injury via ER stress and mitochondria-associated apoptosis pathways[J].Cell Death & Disease,2017,8(10):e3080.
[4] LOPEZ M G,PANDHARIPANDE P,MORSE J,et al.Intraoperative cerebral oxygenation,oxidative injury,and delirium following cardiac surgery[J].Free Radical Biology & Medicine,2017,103(Complete):192-198.
[5] SLAB C,NAA B,NCAB C,et al.The possible roles of necroptosis during cerebral ischemia and ischemia/reperfusion injury[J].Archives of Biochemistry and Biophysics,2020,695:108629.
[6] ARPITA K,ASHISH K,BRYAN M,et al.A serine protease KLK8 emerges as a regulator of regulators in memory:Microtubule protein dependent neuronal morphology and PKA-CREB signaling[J].Scientific Reports,2018,8(1):9928.
[7] MAEDER C I,JAE-ICK K,LIANG X,et al.The THO complex coordinates transcripts for synapse development and dopamine neuron survival[J].Cell,2018,174(6):1436-1449.
[8] GUANL V,XIA O.Potential role of the cAMP/PKA/CREB signalling pathway in hypoxic preconditioning and effect on propofolinduced neurotoxicity in the hippocampus of neonatal rats[J].Molecular Medicine Reports,2019,20(2):1837-1845.
[9] BAI H,ZHAO L,LIU H,et al.Adiponectin confers neuroprotection against cerebral ischemia-reperfusion injury through activating the cAMP/PKA/CREB/BDNF signaling[J].Brain Research Bulletin,2018,143:145-154.
[10] HAUSBURG M A,BANTON K L,ROMAN P E,et al.Effects of propofol on ischemia-reperfusion and traumatic brain injury[J].Journal of Critical Care,2019,56:281-287.
[11] CHEN Y,LI Z.Protective effects of propofol on rats with cerebral ischemia-reperfusion injury via the PI3K/Akt pathway[J].Journal of Molecular Neuroscience,2021,71(4):810-820.
[12] XU F,MA R,ZHANG G,et al.Estrogen and propofol combination therapy inhibits endoplasmic reticulum stress and remarkably attenuates cerebral ischemia-reperfusion injury and OGD injury in hippocampus[J].Biomed Pharmacother,2018,108:1596-1606.
[13] WANG K,RU J,ZHANG H,et al.Melatonin enhances the therapeutic effect of plasma exosomes against cerebral ischemia-induced pyroptosis through the TLR4/NF-κB pathway[J].Frontiers in Neuroscience,2020,14:848.
[14] 闫磊,胡江平,邵新然,等.淫羊藿苷联合冰片对脑缺血-再灌注损伤模型大鼠抗氧化活性、炎症反应和血脑屏障通透性影响[J].陕西中医,2018,39(12):1659-1662.
[15] WAHEED S,KALSEKAR A G,KAMAL A K,et al.Association of plasma levels of nitric oxide oxidative metabolites with acute stroke in patients presenting to the emergency department of a low-middle income country[J].Emergency Medicine International,2019:9206948.
[16] 王剑.乌灵胶囊对脑卒中后抑郁患者血清Hcy、神经细胞因子、单胺类递质代谢和炎症反应的影响[J].陕西中医,2018,39(10):1357-1359.
[17] JIN Z,GUO P,LI X,et al.Neuroprotective effects of irisin against cerebral ischemia/ reperfusion injury via Notch signaling pathway[J].Biomed Pharmacother,2019,120:109452.
[18] LI Y,XIANG L,WANG C,et al.Protection against acute cerebral ischemia/reperfusion injury by leonuri herba total alkali via modulation of BDNF /TrKB/PI3K/Akt signaling pathway in rats[J].Biomed Pharmacother,2021,133:111021.
[19] WANG Y,XIAO G,HE S,et al.Protection against acute cerebral ischemia /reperfusion injury by Qi Shen Yi Qi via neuroinflammatory network mobilization[J].Biomed Pharmacother,2020,125:109945.
[20] MA C,WANG X,XU T Y,et al.Qingkailing injection ameliorates cerebral ischemia-reperfusion injury and modulates the AMPK/NLRP3 inflammasome signalling pathway[J].BMC Complement Altern Med,2019,19(1):320.
[21] SAHINOVIC M M,STRUYS M,ABSALOM A R.Clinical pharmacokin etics and pharmacodynamics of Propofol[J].Clinical Pharmacokinetics,2018,57(12):1539-1558.
[22] Hausburg M A,Banton K L,Roman P E,et al.Effects of propofol on ischemia-reperfusion and traumatic brain injury[J].Journal of Critical Care,2020,56,281-287.
[23] 薛青,赵承天,宋鹏辉,等.丙泊酚抑制脑缺血再灌注损伤大鼠细胞凋亡及其机制[J].临床和实验医学杂志,2017,16(16):1561-1564.
[24] LI P,ZHANG Y,LIU H.The role of Wnt/β-catenin pathway in the protection process by dexmedetomidine against cerebral ischemia/reperfusion injury in rats[J].Life Sciences,2019,236:116921.
[25] YU S J,YU M J,BU Z Q,et al.MicroRNA-670 aggravates cerebral ischemia /reperfusion injury via the Yap pathway[J].Neural Regeneration Research,2021,16(6):1024-1030.
[26] KANDEL E R.The molecular biology of memory:cAMP,PKA,CRE,CREB-1,CREB-2 and CPEB[J].Molecular Brain,2012,5:14.
[27] 梁伟华,蒋淼.丙泊酚减低EZH2对miR-34a抑制效应与肠癌细胞增殖侵袭能力变化的研究[J].陕西医学杂志,2022,51(10):1191-1195.
[28] 官俏兵,韩晨阳,储志远,等.丁苯酞通过激动cAMP/CREB/BDNF信号通路改善小鼠缺血再灌注后认知障碍的作用机制[J].中国临床药理学与治疗学,2019,24(2):152-157.

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备注/Memo

备注/Memo:
基金项目:河北省邯郸市科学技术研究与发展计划项目(1823208074ZC)
更新日期/Last Update: 2024-04-07