PD1经上调心脏巨噬细胞GPR37/JNK/PPAR-γ通路活性减轻大鼠心脏缺血再灌注损伤

曾雅琳; 周沁; 熊青松; 陈运清

doi:10.16016/j.1000-5404.201903197

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PD1经上调心脏巨噬细胞GPR37/JNK/PPAR-γ通路活性减轻大鼠心脏缺血再灌注损伤

基础医学 | 更新时间：2026-01-09

- PD1经上调心脏巨噬细胞GPR37/JNK/PPAR-γ通路活性减轻大鼠心脏缺血再灌注损伤
- Protectin D1 alleviates cardiac ischemia-reperfusion injury in rats by up-regulating GPR37/JNK/PPAR-γ signaling pathway in cardiac macrophages
- 第三军医大学学报 2019年41卷第16期页码：1511-1519
- 作者机构：
  
  400010 重庆，重庆医科大学附属第二医院心内科
- 作者简介：
  
  [ 陈运清，E-mail: chenyunqing.88@163.com CHEN Yunqing, E-mail:chenyunqing.88@163.com
- 基金信息：
  
  国家自然科学基金面上项目(8157070581)
- DOI：10.16016/j.1000-5404.201903197
  中图分类号： R542.2; R963; R977.6
- 收稿：2019-03-25，
  
  修回：2019-05-23，
  
  纸质出版：2019-08-30
- 稿件说明：
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曾雅琳, 周沁, 熊青松, 等. PD1经上调心脏巨噬细胞GPR37/JNK/PPAR-γ通路活性减轻大鼠心脏缺血再灌注损伤[J]. 第三军医大学学报, 2019,41(16):1511-1519.

Yalin ZENG, Qin ZHOU, Qingsong XIONG, et al. Protectin D1 alleviates cardiac ischemia-reperfusion injury in rats by up-regulating GPR37/JNK/PPAR-γ signaling pathway in cardiac macrophages[J]. Journal of Third Military Medical University, 2019, 41(16): 1511-1519.
曾雅琳, 周沁, 熊青松, 等. PD1经上调心脏巨噬细胞GPR37/JNK/PPAR-γ通路活性减轻大鼠心脏缺血再灌注损伤[J]. 第三军医大学学报, 2019,41(16):1511-1519. DOI： 10.16016/j.1000-5404.201903197.

Yalin ZENG, Qin ZHOU, Qingsong XIONG, et al. Protectin D1 alleviates cardiac ischemia-reperfusion injury in rats by up-regulating GPR37/JNK/PPAR-γ signaling pathway in cardiac macrophages[J]. Journal of Third Military Medical University, 2019, 41(16): 1511-1519. DOI： 10.16016/j.1000-5404.201903197.

摘要

目的

探讨保护素(protectin D1

PD1)经GPR37/JNK/PPAR-γ通路减轻心脏缺血再灌注损伤的机制。

方法

6~8周雄性SD大鼠60只(体质量180~220 g)，于术前3日每日经腹腔注射PD1 100 nmol/L或等量生理盐水后，建立大鼠心脏缺血再灌注损伤模型，分为4组：假手术组；缺血再灌注组(IR组)；IR+PD1组；IR+PD1+CB组。各组大鼠于术后6 h、24 h、48 h、14 d采集大鼠心脏标本和血液标本，并分离心脏巨噬细胞蛋白。检测心脏病理改变、心肌酶谱改变、心肌纤维化程度、血清炎症因子表达、心肌细胞吞噬功能、细胞极性改变、上清液炎症因子表达、GPR37/JNK/PPAR-γ信号通路表达。

结果

PD1干预后，大鼠心脏病理改变显著下降、心肌酶谱表达下降(

0.05)，血清IL-1β(86.6±22.4)U/L、TNF-α(89.4±18.2)U/L、IL-6(76.7±15.2)U/L表达下降，IL-10(87.6±18.4)U/L、TGF-β(112.7±22.6)U/L表达升高(

0.05)；PD1处理心脏巨噬细胞后，心脏巨噬细胞对凋亡细胞吞噬增高(

0.05)，M2型极化增加(

0.05)，上清液中IL-1β(109.5±21.6) U/L、TNF-α(95.4±17.8) U/L、IL-6(134.2±27.1) U/L表达下降，IL-10(158.4±31.8)U/L、TGF-β(149.6±27.6)U/L表达升高(

0.05)，GPR37(2.14±0.31)、IRE1α (2.67±0.44)、ATF6 (1.97±0.37)、PERK (2.27±0.67)、p-JNK (1.95±0.39)、PPAR-γ (1.87±0.67)表达上升(

0.05)。

结论

PD1能够减轻心脏缺血再灌注损伤程度，其机制可能是经上调GPR37/JNK/PPAR-γ通路的活性，促进心脏巨噬细胞吞噬功能、M2型极化、抑炎因子表达。

Abstract

Objective

To investigate the mechanism by which protectin D1 (PD1) alleviates cardiac ischemia-reperfusion (IR) injury

via

GPR37/JNK/PPAR-γ signaling pathway.

Methods

Male adult SD rats (6-8 weeks old) were randomly divided into sham-operation group

IR group

IR+PD1 group

and IR+PD1+ cytochalasin B (CB) group. In the latter 3 groups

the rats were subjected to daily intraperitoneal injections of normal saline

PD1 (100 nmol/L)

or PD1 and CB for consecutive 3 days before establishment of cardiac IR injury models. At 6

and 48 h and at 2 weeks after the surgery

the hearts and blood samples were collected from each group

and the cardiac macrophages were isolated and cultured. The cardiac pathologies

changes in cardiac enzyme profile

cardiac fibrosis

serum inflammatory factors

phagocytic function of the cardiac macrophages

changes in the cell polarity

and the expressions of inflammatory factors and GPR37/JNK/ PPAR-γ signaling pathway in cultured cardiac macrophages were detected.

Results

In the rats with cardiac IR injury

PD1 treatment significantly alleviated the cardiac pathologies

lowered the expressions of the cardiac enzymes (

0.05)

decreased the serum levels of IL-1β

TNF-α

and IL-6 while increased the serum levels of IL-10 and TGF-β (

0.05). In the cultured cardiac macrophages

PD1 treatment significantly enhanced their phagocytosis of the apoptotic cells (

0.05) and M2-type polarization (

0.05)

decreased the expressions of IL-1β

TNF-α

IL-6

and increased the expressions of IL-10 and TGF-β (

0.05) and the expressions of GPR37

IRE1α

ATF6

PERK

p-JNK

and PPAR-γ (

0.05).

Conclusion

PD1 can alleviate cardiac IR injury in rats possibly by up-regulating the GPR37/JNK/PPAR-γ signaling pathway to enhance the phagocytic activity of the cardiac macrophages and the expressions of the anti-inflammatory factors.

关键词

Keywords

references

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