[1]张博睿,樊 龙,姚 波,等.右美托咪定在大鼠脑缺血再灌注损伤中的作用及其机制实验研究[J].陕西医学杂志,2024,(11):1474-1477,1482.[doi:DOI:10.3969/j.issn.1000-7377.2024.11.007]
　ZHANG Borui,FAN Long,YAO Bo,et al.Role and mechanism of dexmedetomidine in cerebral ischemia-reperfusion injury in rats[J].,2024,(11):1474-1477,1482.[doi:DOI:10.3969/j.issn.1000-7377.2024.11.007]
点击复制

右美托咪定在大鼠脑缺血再灌注损伤中的作用及其机制实验研究
分享到：

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2024年11期
页码:
1474-1477,1482
栏目:
基础研究
出版日期:
2024-11-05

文章信息/Info

Title:
Role and mechanism of dexmedetomidine in cerebral ischemia-reperfusion injury in rats
作者:
张博睿1; 樊 龙1; 姚 波1; 单 冰1; 王建银2; 赵 静1
(1.陕西省人民医院麻醉科,陕西 西安 710068; 2.西安医学院研究生工作部,陕西 西安 710021)
Author(s):
ZHANG Borui; FAN Long; YAO Bo; SHAN Bing; WANG Jianyin; ZHAO Jing
(Department of Anesthesiology,Shaanxi Provincial People's Hospital,Xi'an 710068,China)
关键词:
脑缺血再灌注损伤;  右美托咪定;  c-Jun氨基末端激酶/核因子-κB信号通路;  神经功能;  应激反应;  大鼠
Keywords:
Cerebral ischemia-reperfusion injury;  Dexmedetomidine;  JNK/NF-κB signaling pathway;  Neurological function;  Stress response;  Rats
分类号:
R -33
DOI:
DOI:10.3969/j.issn.1000-7377.2024.11.007
文献标志码:
A
摘要:
目的:探讨右美托咪定(DEX)在大鼠脑缺血再灌注损伤(CIRI)中的作用及其机制。方法:选取雄性SD大鼠72只,随机分为假手术组、模型组、DEX组,各24只。建立CIRI大鼠模型,DEX组在脑缺血1 h时,经尾静脉注射DEX 100 μg/kg; 其余两组注射等量0.9%氯化钠溶液。评估各组大鼠神经功能缺损情况,测定脑含水量、超氧化物歧化酶(SOD)和丙二醛(MDA)含量。采用TTC染色法检测大鼠脑梗死体积,HE染色观察大鼠脑组织病理学变化。采用TUNEL法检测大鼠海马CA1区神经元凋亡情况。采用Western blot检测大鼠脑组织c-Jun氨基末端激酶(JNK)/核因子-κB(NF-κB)信号通路相关蛋白表达。结果:假手术组大鼠脑组织神经细胞排列整齐,细胞多呈圆形,结构清晰紧密。模型组大鼠神经细胞数量减少,细胞相隔较远且细胞核固缩,排列无序,并可见大量炎症细胞浸润。与模型组比较,DEX组大鼠神经细胞层次较为清楚,细胞数量增加,结构趋于完整,间质水肿状态减轻。与假手术组比较,模型组和DEX组脑含水量、海马CA1区神经细胞凋亡率、脑组织MDA及p-JNK、p65、NF-κB蛋白表达水平明显升高,脑组织SOD水平降低(均P<0.05)。与模型组比较,DEX组Zea Longa评分、脑含水量、脑梗死体积比、海马CA1区神经细胞凋亡率、脑组织MDA及p-JNK、p65、NF-κB蛋白表达水平降低,脑组织SOD水平升高(均P<0.05)。结论:DEX能够恢复CIRI大鼠神经功能,缩小脑梗死灶体积,减轻应激反应,其作用机制可能与JNK/NF-κB信号通路有关。
Abstract:
Objective:To explore the role and mechanism of dexmedetomidine(DEX)in cerebral ischemia-reperfusion injury(CIRI)in rats.Methods:A total of 72 male SD rats were randomly divided into sham operation group,model group and DEX group,with 24 rats each.CIRI rat model was established.DEX group was injected with DEX 100 μg/kg through the tail vein at 1 h after cerebral ischemia.The other two groups were injected with 0.9% sodium chloride solution.The neurofunctional impairment of rats in each group was evaluated,and the contents of brain water content,superoxide dismutase(SOD)and malondialdehyde(MDA)were measured.TTC staining was used to detect the infarct volume of rats.HE staining was used to observe the pathological changes of brain tissue.The apoptosis of hippocampal CA1 was detected by TUNEL method.The expression of c-Jun amino-terminal kinase(JNK)/ nuclear factor-κB(NF-κB)signaling pathway related proteins in rat brain was detected by Western blot.Results:In the sham operation group,the nerve cells were arranged neatly,and the cells were mostly round with clear and compact structure.In the model group,the number of nerve cells decreased,the cells were far apart,the nuclei were shrunk,the arrangement was disorderly,and a large number of inflammatory cells were infiltrated.Compared with the model group,the level of nerve cells in DEX group was more clear,the number of cells increased,the structure tended to be complete,and the state of interstitial edema was reduced.Compared with the sham operation group,the brain water content,the apoptosis rate of nerve cells in the hippocampal CA1 region,the levels of MDA and p-JNK,p65 and NF-κB proteins in the brain tissue were increased,and the level of SOD in the brain tissue was decreased in the model group and the DEX group(all P<0.05).Compared with the model group,the Zea Longa score,brain water content,cerebral infarct volume ratio,neuronal apoptosis rate in hippocampal CA1 region,and the levels of MDA,p-JNK,p65 and NF-κB proteins in brain tissue were decreased,while the level of SOD was increased in the DEX group(all P<0.05).Conclusion:DEX can promote the recovery of neurofunction in CIRI rats,reduce the volume of cerebral infarction and alleviate stress response,and its mechanism may be related to the JNK/NF-κB signaling pathway.

参考文献/References:

[1] 张霞婧,毛肖肖,朱芳芸,等.丙酮酸乙酯通过调控小胶质细胞极化减轻脑缺血再灌注损伤实验研究[J].陕西医学杂志,2022,51(5):520-524.
[2] CHEN M,LIU J,WU W,et al.SIRT1 restores mitochondrial structure and function in rats by activating SIRT3 after cerebral ischemia/reperfusion injury[J].Cell Biol Toxicol,2024,40(1):31.
[3] KANG C,SANG Q,LIU D,et al.Polyphyllin I alleviates neuroinflammation after cerebral ischemia-reperfusion injury via facilitating autophagy-mediated M2 microglial polarization[J].Mol Med,2024,30(1):59.
[4] 张文洁,屈松,吴玉敏,等.右美托咪定作为神经阻滞佐剂的研究进展[J].实用临床医药杂志,2024,28(2):119-123.
[5] 陈金权,赵娟.右美托咪定对缺血性脑损伤大鼠神经功能及认知障碍恢复的影响研究[J].陕西医学杂志,2022,51(2):155-158.
[6] 赵万里,张鹏举,马启斌,等.右美托咪定调控DDR1对大鼠脑缺血/再灌注氧化应激的影响[J].中国药理学通报,2023,39(6):1199-1200.
[7] 刘宗梅,王晓玲,宋发萍,等.基于NF-κB通路研究平肝活血合剂对脑缺血再灌注损伤的作用机制[J].中南药学,2024,22(4):902-907.
[8] 陈浩,张天琦,马骁,等.托里消毒散通过调控NF-κB信号通路对大鼠皮瓣缺血再灌注损伤的影响[J].南京中医药大学学报,2024,40(1):61-67.
[9] ZHU C,WANG D,CHANG C,et al.Dexmedetomidine alleviates blood-brain barrier disruption in rats after cerebral ischemia-reperfusion by suppressing JNK and p38 MAPK signaling[J].Korean J Physiol Pharmacol,2024,28(3):239-252.
[10] LONGA E Z,WEINSTEIN P R,CARLSON S,et al.Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke,1989,20(1):84-91.
[11] DAI F,HU C,LI X,et al.Cav3.2 channel regulates cerebral ischemia/reperfusion injury:A promising target for intervention[J].Neural Regen Res,2024,19(11):2480-2487.
[12] 刘婵娟,桑鹏.针刺调控脑缺血再灌注损伤后钙超载机制研究进展[J].针刺研究,2024,49(3):302-306,314.
[13] 翟阳,莫雪妮,滕红丽,等.壮药双路通脑方对脑缺血再灌注损伤大鼠神经元凋亡的影响[J].中成药,2024,46(3):795-802.
[14] 赵海峰,范鸣玥,陈亮,等.盐酸右美托咪定通过抑制细胞焦亡发挥脑缺血再灌注损伤保护作用[J].中国药理学与毒理学杂志,2023,37(10):744-752.
[15] 杨毅峰,叶楠,王琳,等.右美托咪定抗缺血再灌注损伤的信号通路[J].中国组织工程研究,2024,28(9):1464-1469.
[16] 李显碧,刘尚升,肖兵,等.右美托咪定通过沉默信息调节因子1/核转录因子信号通路调控脑梗死大鼠海马组织炎症机制研究[J].陕西医学杂志,2024,53(1):23-27.
[17] 石青青,刘玲,马欣旭,等.慢性束缚应激对小鼠海马PD-1/PD-L1表达水平及炎症反应和氧化应激信号通路的影响[J].空军军医大学学报,2023,44(11):1052-1058.
[18] CHEN X,YAO N,MAO Y,et al.Activation of the Wnt/β-catenin/CYP1B1 pathway alleviates oxidative stress and protects the blood-brain barrier under cerebral ischemia/reperfusion conditions[J].Neural Regen Res,2024,19(7):1541-1547.
[19] 罗佳,吴宇,刘京东,等.香叶醇通过调控Nrf2/HO-1途径调节氧化应激减轻大鼠脑缺血/再灌注损伤[J].中国药理学通报,2024,40(3):431-439.
[20] 马娴,高萍,刘真一,等.补阳还五汤减轻氧化应激保护脑缺血再灌注损伤大鼠血脑屏障的作用研究[J].中国比较医学杂志,2024,34(3):75-84,101.
[21] 蒋洁,刘娟,于燕艳,等.灸法预处理减轻脑缺血再灌注模型大鼠氧化应激损伤的机制[J].中国组织工程研究,2024,28(16):2488-2493.
[22] 杨文君,董盛,陈雨菡,等.黄芪-丹参对脑缺血/再灌注损伤小鼠氧化应激的影响[J].中医学报,2024,39(5):1045-1052.
[23] 岳云,王佩佩,袁兆鹤,等.巴豆霜干预脑缺血再灌注损伤大鼠皮质区JNK/p38 MAPK及神经元凋亡的机制[J].中国组织工程研究,2024,28(8):1186-1192.
[24] 杨毅峰,叶楠,王琳,等.右美托咪定抗缺血再灌注损伤的信号通路[J].中国组织工程研究,2024,28(9):1464-1469.
[25] 刘宗梅,王晓玲,宋发萍,等.基于NF-κB通路研究平肝活血合剂对脑缺血再灌注损伤的作用机制[J].中南药学,2024,22(4):902-907.
[26] 赵莹,赵晶.酒石酸布托啡诺基于JNK/NF-κB信号通路对大鼠脑缺血再灌注损伤的改善作用[J].河北医药,2023,45(3):325-329.

相似文献/References:

[1]薛璋明,周绍文△,张 娟,等.羟考酮联合右美托咪定应用于区域麻醉镇静临床观察[J].陕西医学杂志,2020,49(2):231.
　XUE Zhangming,ZHOU Shaowen,ZHANG Juan,et al.Clinical observation of sedation under regional anesthesia with oxycodone combined with dexmedetomidine[J].,2020,49(11):231.
[2]杨 昊,郭 聪△.右美托咪定在降低老年腰椎手术患者术后认知功能障碍发生率中的应用[J].陕西医学杂志,2020,49(5):608.
　YANG Hao,GUO Cong..Application of dexmedetomidine in reducing the incidence of postoperative cognitive dysfunction in elderly patients undergoing lumbar surgery[J].,2020,49(11):608.
[3]张 祎,陈 权,尚 游.体温保护联合右美托咪定预防老年脊柱手术患者术后谵妄及寒战临床效果观察[J].陕西医学杂志,2021,50(3):308.[doi:DOI:10.3969/j.issn.1000-7377.2021.03.013]
[4]王 月,刘佳俊,王 雷,等.缺血后处理通过升高血清腺苷水平减轻脑缺血再灌注损伤的实验研究[J].陕西医学杂志,2021,50(7):789.[doi:DOI:10.3969/j.issn.1000-7377.2021.07.005]
　WANG Yue,LIU Jiajun,WANG Lei,et al.Experimental study of ischemic postconditioning on reducing cerebral ischemia-reperfusion injury by increasing adenosine[J].,2021,50(11):789.[doi:DOI:10.3969/j.issn.1000-7377.2021.07.005]
[5]任学智,田芳玲,李 丹.七氟烷吸入全麻后持续泵入右美托咪定对腹腔镜胆囊切除患者镇痛效果研究[J].陕西医学杂志,2021,50(8):1007.[doi:DOI:10.3969/j.issn.1000-7377.2021.08.026]
[6]郭 聪,杨 昊.罗哌卡因复合不同剂量右美托咪定腹横肌平面阻滞对胃肠道腹腔镜手术患者镇痛及术后认知功能的影响[J].陕西医学杂志,2021,50(8):1011.[doi:DOI:10.3969/j.issn.1000-7377.2021.08.027]
　GUO Cong,YANG Hao.Effect of ropivacaine combined with different doses of dexmedetomidine in transversus abdominis plane block on intraoperative analgesia and the incidence of postoperative cognitive dysfunction in gastrointestinal laparoscopic surgery[J].,2021,50(11):1011.[doi:DOI:10.3969/j.issn.1000-7377.2021.08.027]
[7]单兆亚,王 波.右美托咪定调控急性痛风性关节炎模型大鼠血清炎性因子水平及滑膜功能效果研究[J].陕西医学杂志,2021,50(9):1052.[doi:DOI:10.3969/j.issn.1000-7377.2021.09.003]
　SHAN Zhaoya,WANG Bo.Effect of dexmedetomidine on regulating serum inflammatory factors and synovial function in rats with acute gouty arthritis[J].,2021,50(11):1052.[doi:DOI:10.3969/j.issn.1000-7377.2021.09.003]
[8]王 瑗,冯建梅,卫白杨.右美托咪定对坐骨神经慢性压迫损伤模型大鼠神经病理性疼痛的缓解作用及机制研究[J].陕西医学杂志,2021,50(12):1492.[doi:DOI:10.3969/j.issn.1000-7377.2021.12.006]
　WANG Yuan,FENG Jianmei,WEI Baiyang.Alleviating effect and mechanism of dexmedetomidine on chronic neuropathic pain in rat model with chronic compression injury of sciatic nerve[J].,2021,50(11):1492.[doi:DOI:10.3969/j.issn.1000-7377.2021.12.006]
[9]梁 赟,佘 濛,高子军,等.智能自控静脉镇痛泵用于腰椎后路融合术后患者镇痛效果研究[J].陕西医学杂志,2022,51(2):180.[doi:DOI:10.3969/j.issn.1000-7377.2022.02.012]
　LIANG Yun,SHE Meng,GAO Zijun,et al.Analgesic effect of smart-PCIA on patients after posterior lumbar fusion[J].,2022,51(11):180.[doi:DOI:10.3969/j.issn.1000-7377.2022.02.012]
[10]王兴程,张向宁,侯崇智,等.右美托咪定在脓毒症治疗中的作用及机制研究进展[J].陕西医学杂志,2022,51(3):382.[doi:DOI:10.3969/j.issn.1000-7377.2022.03.028]
　WANG Xingcheng,ZHANG Xiangning,HOU Chongzhi,et al.Research progress on the role and mechanism of dexmedetomidine in the treatment of sepsis[J].,2022,51(11):382.[doi:DOI:10.3969/j.issn.1000-7377.2022.03.028]

备注/Memo

备注/Memo:
基金项目:陕西省自然科学基础研究计划项目(2023-JC-QN-0951); 陕西省重点研发计划项目(2022SF-264)
更新日期/Last Update: 2024-11-04