肝素结合表皮生长因子样生长因子（HB-EGF）通过 JNK 和 p38/MAPK 依赖性途径抗凋亡保护肠缺血再灌注损伤。

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) protected intestinal ischemia-reperfusion injury through JNK and p38/MAPK-dependent pathway for anti-apoptosis.

机构信息

Division of Pediatric Surgery, Department of Pediatrics, Chang Gung Children's Medical Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.

Division of Pediatric Gastroenterology, Department of Pediatrics, Chang Gung Children's Medical Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.

出版信息

Pediatr Neonatol. 2019 Jun;60(3):332-336. doi: 10.1016/j.pedneo.2018.08.003. Epub 2018 Aug 17.

DOI:10.1016/j.pedneo.2018.08.003

PMID:30455099

Abstract

BACKGROUND

Heparin-Binding Epidermal Growth Factor-Like Growth Factor (HB-EGF) is a potent cytoprotective factor in various body systems, including gastrointestinal tract. In this study, we intended to examine whether HB-EGF exerts its protective effects through MAPK dependent anti-apoptosis after intestinal I/R injury.

METHODS

We randomly divided 30 laboratory 30 rats into 5 groups: (A) normal control group, (B) ischemia group with normal saline, (C) I/R group with normal saline, (D) ischemia group with HB-EGF (400 ug/kg), and (E) I/R group with HB-EGF (400 ug/kg). With Western blotting study, we determined JNK and p38/MAPK pathway and caspase-3 activity protein levels using Western analyses.

RESULTS

The JNK phosphorylation protein levels increased after intestinal ischemia or intestinal reperfusion phase, and HB-EGF pre-treatment was significantly decreased in JNK phosphorylation protein levels (p < 0.01). We found that p38 protein levels was increased after intestinal reperfusion phase, and that HB-EGF pre-treatment significantly decreased p38 protein levels (p < 0.01). The expression protein level of caspase 3 was increased after intestinal ischemia or intestinal reperfusion phase. HB-EGF pre-treatment significantly decreased Caspase 3 proteins. (p < 0.01).

CONCLUSION

Our study revealed that pre-treatment of HB-EGF decreased the amount of activity of JNK and p38/MAPK pathway and caspase-3 protein after intestinal I/R injury. These results may further support that the cytoprotective of HB-EGF after I/R injury could be through anti-apoptotic effect of activity of JNK and p38/MAPK pathway.

摘要

背景

肝素结合表皮生长因子样生长因子（HB-EGF）是一种在包括胃肠道在内的各种身体系统中具有强大细胞保护作用的因子。在本研究中，我们旨在研究 HB-EGF 是否通过 MAPK 依赖性抗细胞凋亡发挥其在肠 I/R 损伤后的保护作用。

方法

我们将 30 只实验室大鼠随机分为 5 组：（A）正常对照组，（B）生理盐水缺血组，（C）生理盐水 I/R 组，（D）HB-EGF（400ug/kg）缺血组，和（E）HB-EGF（400ug/kg）I/R 组。通过 Western 印迹研究，我们使用 Western 分析确定了 JNK 和 p38/MAPK 通路和 caspase-3 活性蛋白水平。

结果

肠缺血或肠再灌注期 JNK 磷酸化蛋白水平增加，HB-EGF 预处理后 JNK 磷酸化蛋白水平明显降低（p<0.01）。我们发现肠再灌注期 p38 蛋白水平增加，HB-EGF 预处理后 p38 蛋白水平明显降低（p<0.01）。肠缺血或肠再灌注期 caspase 3 表达蛋白水平增加，HB-EGF 预处理后 Caspase 3 蛋白明显减少（p<0.01）。