脂联素通过抑制线粒体融合与分裂失衡减轻慢性间歇低氧所致大鼠胰岛细胞损伤

何灿; 张希龙; 张蔷; 葛路遥; 丁文筱

doi:10.24920/003834

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脂联素通过抑制线粒体融合与分裂失衡减轻慢性间歇低氧所致大鼠胰岛细胞损伤

中国医学科学杂志（英文版） 2021年36卷第3期页码：225-233

论著 | Updated：2024-04-10

- 脂联素通过抑制线粒体融合与分裂失衡减轻慢性间歇低氧所致大鼠胰岛细胞损伤
- Affiliations：
  
  1. 1Department of Pulmonary and Critical Care Medicine, Zhongda Hospital, School of Medicine Southeast University, Nanjing 210009, China
  2. 2Department of Pulmonary and Critical Care Medicine, the First Affiliated; Hospital, Nanjing Medical University, Nanjing 210029, China
- Author bio：
  
  *Tel: 86-13605192643; E-mail: wenxiaoding@163.com
- Funds：
  
  This work was supported by the National Natural Science Foundation of China;国家自然科学基金(81700090);the General Topics of Medical Science and Technology Development of Nanjing;南京市医学科技发展项目(YKK17237)
- DOI：10.24920/003834
  中图分类号：
- 录用日期：2020-12-9，
  
  纸质出版日期：2021-08-04
- Accepted：
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何灿, 张希龙, 张蔷, 等. 脂联素通过抑制线粒体融合与分裂失衡减轻慢性间歇低氧所致大鼠胰岛细胞损伤[J]. 中国医学科学杂志（英文版）, 2021,36(3):225-233.

He Can, Zhang Xilong, Zhang Qiang, et al. Adiponectin Ameliorated Pancreatic Islet Injury Induced by Chronic Intermittent Hypoxia through Inhibiting the Imbalance in Mitochondrial Fusion and Division[J]. Chinese medical sciences journal, 2021, 36(3): 225-233.
何灿, 张希龙, 张蔷, 等. 脂联素通过抑制线粒体融合与分裂失衡减轻慢性间歇低氧所致大鼠胰岛细胞损伤[J]. 中国医学科学杂志（英文版）, 2021,36(3):225-233. DOI： 10.24920/003834.

He Can, Zhang Xilong, Zhang Qiang, et al. Adiponectin Ameliorated Pancreatic Islet Injury Induced by Chronic Intermittent Hypoxia through Inhibiting the Imbalance in Mitochondrial Fusion and Division[J]. Chinese medical sciences journal, 2021, 36(3): 225-233. DOI： 10.24920/003834.

摘要

目的

探讨脂联素（adiponectin

APN）对慢性间歇低氧（chronic intermittent hypoxia

CIH）所致大鼠胰岛损伤的保护作用及相关机制。

方法

60只SD大鼠随机分为3组：对照（normal contral

NC）组、CIH组及CIH+APN组。5周的CIH暴露后

我们对大鼠进行口服葡萄糖耐量试验（oral glucose tolerance test

OGTT）及胰岛素释放试验（insulin released test

IRT）。提取胰岛

检测并比较三组间大鼠胰岛ATP水平

线粒体膜电位（mitochondrial membrane potential

MMP）水平

活性氧（reactive oxygen species

ROS）水平

线粒体三羧酸循环相关酶基因

Ant1

、

Hmox1

和

Cox4i1

表达水平

线粒体融合与分裂相关蛋白及基因DRP1、FIS1、MFN1和OPA1表达水平

及胰岛线粒体凋亡相关蛋白BAX、BCL-2、cleaved Caspase-3、cleaved PARP表达水平。

结果

CIH暴露5周后

OGTT及IRT试验显示各组大鼠在0分钟、20分钟、30分钟、60分钟及120分钟的血糖及胰岛素水平均无明显差异。然而我们发现CIH暴露后

大鼠胰岛ROS水平增加

ATP及MMP水平下降

Ant1

、

Hmox1

和

Cox4i1

基因表达水平下降

MFN1和OPA1蛋白及基因表达水平下降

DRP1、FIS1蛋白及基因表达水平增加

cleaved Caspase-3和cleaved PARP蛋白表达水平增加

BCL-2/BAX蛋白表达水平比率下降

三组间差异均有统计学显著性。CIH+APN组上述胰岛损伤相关的指标测量值均明显改善。

结论

APN通过抑制线粒体融合与分裂失衡减轻CIH所致大鼠胰岛线粒体损伤

进而减轻大鼠胰岛损伤。

Abstract

Objective

This study aimed to assess the protective value of adiponectin (APN) in pancreatic islet injury induced by chronic intermittent hypoxia (CIH).

Methods

Sixty rats were randomly divided into three groups: normal control (NC) group

CIH group

and CIH with APN supplement (CIH+APN) group. After 5 weeks of CIH exposure

we conducted oral glucose tolerance tests (OGTT) and insulin released test (IRT)

examined and compared the adenosine triphosphate (ATP) levels

mitochondrial membrane potential (MMP) levels

reactive oxygen species (ROS) levels

enzymes gene expression levels of

Ant1

Hmox1

and

Cox4i1

which represented mitochondrial tricarboxylic acid cycle function

the protein and gene expression levels of DRP1

FIS1

MFN1

and OPA1 which represented mitochondrial fusion and division

and the protein expression levels of BAX

BCL-2

cleaved Caspase-3

and cleaved PARP which represented mitochondrial associated apoptosis pathway of pancreatic islet.

Results

OGTT and IRT showed blood glucose and insulin levels had no differences among the NC

CIH and CIH+APN groups (both

0.05) at 0 min

20 min

30 min

60 min

120 min. However

we found that compared to NC group

CIH increased the ROS level

reduced ATP level and MMP level. The islets of CIH exposed rats showed reduced gene expression levels of

Ant1

Hmox1

and

Cox4i1

decreased protein and gene expression levels of MFN1 and OPA1

increased protein and gene expression levels of DRP1 and FIS1

increased protein expression levels of cleaved Caspase-3 and cleaved PARP

with lower ratio of BCL-2/BAX at protein expression level. All the differences among three groups were statistically significant. APN treated CIH rats showed mitigated changes in the above measurements associated with islet injuries.

Conclusion

APN may ameliorate the pancreatic islet injury induced by CIH via inhibiting the imbalance in mitochondrial fusion and division.

关键词

Keywords

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