大鼠脑组织sigma-1受体表达与心肺复苏后脑损伤相关

doi:10.16352/j.issn.1001-6325.2025.09.1200

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (9): 1200-1207.doi: 10.16352/j.issn.1001-6325.2025.09.1200

大鼠脑组织sigma-1受体表达与心肺复苏后脑损伤相关

赵海燕^#, 王怡洁^#, 刘荣, 杨吉林, 李婷, 朱晓琳, 秦佳宏^*

昆明医科大学第一附属医院老年重症医学科,云南昆明 650032

收稿日期:2025-03-06 修回日期:2025-07-01 发布日期:2025-08-27
通讯作者: ^*drqinjh@sina.com
作者简介:^#对本文有相同贡献
基金资助:
昆明医科大学联合专项(202201AY070001-060);昆明医科大学第一附属医院博士启动基金(2018BS003)

Sigma-1 receptor expression in rat brain tissue is correlated with brain injury after cardiopulmonary resuscitation

ZHAO Haiyan^#, WANG Yijie^#, LIU Rong, YANG Jilin, LI Ting, ZHU Xiaolin, QIN Jiahong^*

Department of Geriatric Critical Care Medicine, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China

Received:2025-03-06 Revised:2025-07-01 Published:2025-08-27
Contact: ^*drqinjh@sina.com

摘要/Abstract

摘要： 目的初步探索sigma-1受体(Sig-1R)对心脏骤停复苏后大鼠脑组织功能的影响。方法将大鼠随机分为假手术组(sham组,n=20)、复苏后6 h(PR 6 h组,n=20),12 h(PR 12 h组,n=20)和24 h组(PR 24 h组,n=20)。后3组以窒息法诱导大鼠心脏骤停,心脏骤停6 min后进行心肺复苏。分别于复苏后6、12和24 h对大鼠进行神经功能缺损评分;之后处死大鼠,Western blot及免疫组化检测脑组织中Sig-1R蛋白、线粒体功能指标、内质网应激指标、细胞凋亡指标表达,并评估Sig-1R与线粒体、内质网应激和凋亡指标的相关性。结果与假手术组相比,大鼠在PR 6、12和24 h时,神经功能缺损评分、Sig-1R蛋白表达、脑组织腺嘌呤核苷三磷酸(ATP)浓度和线粒体膜电位(MMP)水平逐渐降低(P＜0.05);CHOP蛋白、激活型cleaved caspase-12和cleaved caspase-3蛋白表达均持续升高(P＜0.05)。此外,Sig-1R分别与脑组织内质网应激和细胞凋亡呈负相关(P＜0.05)、与线粒体膜电位水平呈正相关(P＜0.05)。结论大鼠脑组织Sig-1R蛋白表达与心肺复苏后脑损伤相关,可能通过调节线粒体功能和内质网应激发挥神经元保护作用。

关键词: 心脏骤停后心肺复苏, 全脑缺血/再灌注损伤, sigma-1受体, 线粒体, 内质网应激

Abstract: Objective To explore the effects of sigma-1 receptor(Sig-1R) on brain function in rats after cardiopulmonary resuscitation and its protective role in brain injury. Methods Rats were randomly assigned to four groups with 20 in each: sham-operated control (sham group), 6-hour post-resuscitation (PR 6 h group),12-hour post-resuscitation (PR 12 h group)and 24-hour post-resuscitation (PR 24 h group). In the latter three groups, cardiac arrest was induced by asphyxiation, and cardiopulmonary resuscitation was performed 6 minutes after cardiac arrest. The rats were scored for neurological deficits at 6, 12 and 24 hrs after resuscitation, respectively; after that, the rats were executed, and the expression of Sig-1R protein, mitochondrial function index, and endoplasmic reticulum stress index apoptosis index were detected by Western blot and immunohistochemistry. The correlation between Sig-1R and mitochondrial, endoplasmic reticulum stress and apoptosis indexes was evaluated. Results Compared with the sham-operated group, the rats in test group showed a gradual decrease in neurological deficit scores, Sig-1R protein expression, brain tissue adenosine triphosphate(ATP) concentration and mitochondrial membrane potential(MMP) levels at 6,12, and 24 hrs of PR(P＜0.05); CHOP protein, activated cleaved caspase-12 and cleaved caspase-3 protein expression were consistently elevated (P＜0.05). In addition, Sig-1R was negatively correlated with brain tissue endoplasmic reticulum stress and apoptosis(P＜0.05) but positively correlated with mitochondrial membrane potential level (P＜0.05). Conclusions Sig-1R expression in rat brain tissue correlates with brain injury after cardiopulmonary resuscitation and potential mechanism seems to be neuronal protection through modulating mitochondrial function and endoplasmic reticulum stress.

Key words: cardiopulmonary resuscitation after cardiac arrest, global cerebral ischemia-reperfusion injury, sigma-1 receptor, mitochondria, endoplasmic reticulum stress

中图分类号:

R543.5

赵海燕, 王怡洁, 刘荣, 杨吉林, 李婷, 朱晓琳, 秦佳宏. 大鼠脑组织sigma-1受体表达与心肺复苏后脑损伤相关[J]. 基础医学与临床, 2025, 45(9): 1200-1207.

ZHAO Haiyan, WANG Yijie, LIU Rong, YANG Jilin, LI Ting, ZHU Xiaolin, QIN Jiahong. Sigma-1 receptor expression in rat brain tissue is correlated with brain injury after cardiopulmonary resuscitation[J]. Basic & Clinical Medicine, 2025, 45(9): 1200-1207.

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大鼠脑组织sigma-1受体表达与心肺复苏后脑损伤相关

Sigma-1 receptor expression in rat brain tissue is correlated with brain injury after cardiopulmonary resuscitation

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