艾司洛尔对脓毒症大鼠心肌细胞凋亡影响的实验研究

思飞; 甄玲玲; 王映珍; 张蓓; 张鸿彬; 滕靖茜; 马莉

doi:10.16016/j.1000-5404.202002145

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艾司洛尔对脓毒症大鼠心肌细胞凋亡影响的实验研究

基础医学 | 更新时间：2026-01-09

- 艾司洛尔对脓毒症大鼠心肌细胞凋亡影响的实验研究
- Effects of esmolol on cardiomyocyte apoptosis in septic rats
- 第三军医大学学报 2020年42卷第13期页码：1292-1300
- 作者机构：
  
  1.730030 兰州，兰州大学第二临床医学院
  2.730030 兰州，兰州大学第二医院急危重症科3病区
- 作者简介：
  
  [ 马莉, E-mail：Mali1105@126.com MA Li, E-mail: mali1105@126.com
- 基金信息：
  
  兰州大学第二医院萃英科技创新计划面上项目(CY-2018-MS03)
- DOI：10.16016/j.1000-5404.202002145
  中图分类号： R322.11;R631;R972.2
- 收稿：2020-02-21，
  
  修回：2020-04-04，
  
  纸质出版：2020-07-15
- 稿件说明：
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思飞, 甄玲玲, 王映珍, 等. 艾司洛尔对脓毒症大鼠心肌细胞凋亡影响的实验研究[J]. 第三军医大学学报, 2020,42(13):1292-1300.

Fei SI, Lingling ZHEN, Yingzhen WANG, et al. Effects of esmolol on cardiomyocyte apoptosis in septic rats[J]. Journal of Third Military Medical University, 2020, 42(13): 1292-1300.
思飞, 甄玲玲, 王映珍, 等. 艾司洛尔对脓毒症大鼠心肌细胞凋亡影响的实验研究[J]. 第三军医大学学报, 2020,42(13):1292-1300. DOI： 10.16016/j.1000-5404.202002145.

Fei SI, Lingling ZHEN, Yingzhen WANG, et al. Effects of esmolol on cardiomyocyte apoptosis in septic rats[J]. Journal of Third Military Medical University, 2020, 42(13): 1292-1300. DOI： 10.16016/j.1000-5404.202002145.

摘要

目的

观察短效、高选择性β1受体阻滞剂艾司洛尔对脓毒症大鼠心肌细胞凋亡的影响作用

并探讨可能机制。

方法

63只雄性Wistar大鼠采用随机数字表法分为假手术组(Sham组)

脓毒症组(CLP组)和艾司洛尔组(ES组)

再根据时间点不同随机分为6、12 h和24 h 3个亚组

每亚组7只。Sham组仅开腹翻动盲肠

CLP和ES组均采用盲肠结扎穿孔术(cecal ligation and puncture

CLP)建立脓毒症模型后股静脉置管。Sham、CLP组以1 mL/h速度持续泵入0.9%氯化钠溶液6 h。ES组以1 mL/h速度持续泵入艾司洛尔稀释液

共6 h。造模成功后于6、12 h及24 h时间点处死大鼠

采集并处理标本。ELISA法检测血清TNF-α和BNP水平。WST-1法检测心肌组织SOD活力。分光光度法检测心肌组织MDA含量。Western blot检测心肌组织Caspase-3

Bcl-2

Bax等蛋白的表达。透射电镜观察心肌线粒体结构损伤情况。

结果

与Sham组各时间点相比

CLP、ES组血清TNF-α、BNP水平升高

心肌MDA含量增加

促凋亡蛋白Caspase-3、Bax表达增加(

0.05)。除ES24h组BNP水平较CLP24h组差异无统计学意义(

0.05)外

与CLP组各时间点相比

ES组血清TNF-α、BNP水平降低

心肌MDA含量减少

Caspase-3、Bax等促凋亡蛋白表达减少(

0.05)。与Sham组各时间点相比

CLP、ES组心肌SOD含量和抗凋亡蛋白Bcl-2表达均减少(

0.05)。与CLP组各时间点相比

ES组心肌SOD含量和抗凋亡蛋白Bcl-2表达均增加(

0.05)。电镜下

Sham组各时间点线粒体结构基本正常。CLP组线粒体结构损伤程度最严重

且损伤程度随时间点推移逐渐加重

而ES组各时间点心肌线粒体结构损伤均较CLP组减轻。

结论

艾司洛尔可通过抑制脓毒症大鼠心肌细胞凋亡

在一定程度上改善心功能。机制可能为艾司洛尔通过抑制凋亡启动因子TNF-α

调节Bcl-2、Bax、Caspase-3等凋亡相关蛋白表达而抑制细胞凋亡过程

同时减轻了既是凋亡伴随过程又是凋亡重要启动因素的氧化应激反应

保护了凋亡与氧化应激损伤的靶细胞器线粒体结构。

Abstract

Objective

To investigate the effect of esmolol

a short-acting

highly selective β-blocker

on cardiomyocyte apoptosis in septic rats and its possible mechanism.

Methods

A total of 63 male Wistar rats were randomly divided into sham operation group (Sham group)

sepsis group (CLP group)

and esmolol group (ES group). Each group was further divided into 6-

12-

and 24-hour subgroups. The rats of the Sham group were given sham surgery only

and those of the CLP and ES groups underwent cecal ligation and puncture (CLP) to establish sepsis model. The Sham group and the CLP group were continuously infused with 0.9% sodium chloride solution at a speed of 1 mL/h by micropump for 6 h

while the ES group was continuously infused with 15 mg/kg·h esmolol diluted solution at 1 mL/h for 6 h. Then the rats were sacrificed at 6

12 and 24 h after successful modeling

and the heart specimens were collected. Serum TNF-α and BNP levels were measured by ELISA. Water soluble tetrazolium (WST-1) method was used to detect SOD activity

and spectrophotometry to determine MDA content in myocardial tissue. The expression levels of Caspase-3

Bcl-2

Bax and other proteins in myocardial tissue were detected by Western blotting. Transmission electron microscopy was performed to observe the morphology and structure of myocardial mitochondria.

Results

Compared with the levels at the same time points in Sham group

the serum TNF-α and BNP levels

MDA content

and expression levels of apoptotic proteins such as Caspase-3 and Bax were significantly increased in the CLP and ES groups (

0.05). Except the level of BNP in ES24h group was not significantly different than that in CLP24h group (

0.05)

ES group had obviously decreased serum TNF-α and BNP levels

MDA content

and expression levels of Caspase-3 and Bax when compared with those in the CLP group at same time points (

0.05). The SOD activity and Bcl-2 level were remarkably higher in the CLP and ES groups at the same time points (

0.05)

and the activity and levels were increased in the ES group than the CLP group at all time points (

0.05). Under a transmission electron microscope

myocardial fibers and mitochondria were almost intact in the Sham group at all time points; the damages were the most severe in the CLP group

and the severity was deteriorated gradually with time elapse

while the conditions became alleviated in the ES group at each time point.

Conclusion

Esmolol partially improves cardiac function in septic rats by inhibiting cardiomyocyte apoptosis. The mechanism may be due to its inhibition in apoptosis initiation factor TNF-α and regulation in the expression of apoptosis-related proteins such as Bcl-2

Bax

and Caspase-3

and reduction of the oxidative stress response as well. It mediates both the accompanying process of apoptosis and an important initiator of apoptosis

and protects the mitochondrial structure of target organelles damaged by apoptosis and oxidative stress.

关键词

Keywords

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