XMU-MP-1预处理改善心脏骤停后大鼠心肌功能障碍
XMU-MP-1 pretreatment improves myocardial dysfunction in rats after cardiac arrest
关雪昊 1孙凡 1何宇玲 1杨肇谦 1刘宝山 2孙晓彤 1隽兆东1
作者信息
- 1. 山东第二医科大学,麻醉学院,山东省高等学校麻醉与重症医学实验室,山东潍坊 261053
- 2. 山东第二医科大学第一附属医院潍坊市人民医院心内科,山东潍坊 261053
- 折叠
摘要
目的 评价XMU-MP-1预处理在心脏骤停后大鼠心功能保护中的作用.方法 将健康SD大鼠随机分为6组:假手术组(Sham组,n=6)、常规复苏组(CA-CPR组,n=6)、溶剂对照组(DMSO组,n=6)、XMU 1 mg/kg组(n=6)、XMU 3 mg/kg组(n=6)、XMU 5 mg/kg(n=6).采用窒息法构建心脏骤停模型.超声检测左室短轴缩短率(left ventricular fraction shortening,LVFS)和左室射血分数(left ventricular ejection fraction,LVEF).苏木精-伊红染色观察心肌组织的形态变化.TUNEL染色检测术后细胞凋亡情况.DHE染色评价活性氧含量变化.电镜观察线粒体结构变化.蛋白免疫印迹检测P-MST1/2表达.结果 与Sham组相比,CA-CPR组与DMSO组大鼠心肌纤维断裂、心肌细胞与间质水肿增加、炎症细胞浸润;心肌细胞凋亡率、活性氧表达增加,线粒体评分下降;XMU 1 mg/kg,XMU 3 mg/kg,XMU 5 mg/kg组均可改善上述变化,XMU 3 mg/kg组改善最明显.超声检测发现,与基础LVEF、LVFS相比,复苏后LVEF、LVFS 均下降;组间比较发现,XMU 1 mg/kg,XMU 3 mg/kg,XMU 5 mg/kg 增加 LVEF、LVFS,3 mg/kg 组最明显.与Sham组相比,CA-CPR组与DMSO组P-MST1/2表达升高;与CA-CPR组相比,XMU 3 mg/kg组表达降低.结论 XMU-MP-1预处理能够改善大鼠心脏骤停后的心脏功能,可能与抑制MST1/2、减轻氧化应激和调节线粒体功能有关.
Abstract
Objective To evaluate the effect of XMU-MP-1 preconditioning on post-cardiac arrest myocardial dysfunction.Methods The healthy SD rats were randomly divided into 6 groups:the sham group(n=6),cardiac arrest and cardiopulmonary resuscitation group(n=6),solvent control group(n=6),drug low dose group(XMU 1 mg/kg,n=6),drug medium dose group(XMU 1 mg/kg,n=6),and drug high dose group(XMU 1 mg/kg,n=6).The cardiac arrest model was induced by asphyxia.Left ventricular fraction shortening(LVFS)and left ventricular ejection fraction(LVEF)were measured by echocardiography.Morphological changes were observed by HE staining,cardiomyocyte apoptosis was measured by TUENL assay.ROS content was evaluated by DHE staining.Mitochondria were detected in a transmission electron microscope.P-MST1/2 expression was detected by protein immunoblotting.Results Compared with the Sham group,myocardial fiber fracture,cardiomyocyte and interstitial edema increased and inflammatory cell infiltration increased,cardiomyocyte apoptosis rate,ROS expression increased and the mitochondrial score decreased in the cardiac arrest and cardiopulmonary resuscitation group and solvent control group.The XMU 1 mg/kg、XMU 3 mg/kg、XMU 5mg/kg improved the above changes,with the most obvious improvement in the XMU 3 mg/kg group.LVEF and LVFS were decreased in all group compared with basal LVEF and LVFS.LVEF and LVFS increased in the XMU 1 mg/kg、XMU 3 mg/kg、XMU 5 mg/kg group.It was most evident in the XMU 3 mg/kg group.Compared with the Sham group,P-MST1/2 expression was increased in the CA-CPR group;and its expression reduced in XMU 3 mg/kg group.Conclusions XMU-MP-1 pretreatment attenuated post-cardiac arrest myocardial dysfunction,and may be by inhibiting MST1/2,inhibiting oxidative stress and regulating mitochondrial function.
关键词
心脏骤停后心功能障碍/氧化应激/线粒体损伤Key words
Post-cardiac arrest myocardial dysfunction/Oxidative stress/Mitochondrial damage引用本文复制引用
基金项目
山东省自然科学基金面上项目(ZR2020MH017)
山东省自然基金青年项目(ZR2021QH262)
山东省自然基金青年项目(ZR2020QH005)
出版年
2024
国家科技期刊平台
NSTL
万方数据