- 作者: Yikui Tian; Wenjuan Zhang; Dachuan Xia; Paul Modi; Degang Liang; Minxin Wei
- 作者服務機構: Department of Cardiovascular Surgery, Tianjin Medical University General Hospital, Tianjin, Mainland China.
- 中文摘要: --
- 英文摘要:
Background: Postconditioning (PostC) inhibits myocardial apoptosis after
ischemia-reperfusion (I/R) injury. The JAK2-STAT3 pathway has anti-apoptotic effects and
plays an essential role in the late protection of preconditioning. Our aim was to investigate
the anti-apoptotic effect of PostC after prolonged reperfusion and the role of the
JAK2-STAT3 pathway in the anti-apoptotic effect of PostC.
Methods: Wistar rats were subjected to 30 minutes ischemia and 2 or 24 hours (h)
reperfusion, with or without PostC (three cycles of 10 seconds reperfusion and 10 seconds
reocclusion at the onset of reperfusion). Separate groups of rats were treated with a JAK2
inhibitor (AG490) or a PI3K inhibitor (wortmannin) 5 minutes before PostC.
Immunohistochemistry was used to analyze Bcl-2 protein levels after reperfusion. mRNA
levels of Bcl-2 were detected by qRT-PCR. TTC staining was used to detect myocardial
infarction size. Myocardial apoptosis was evaluated by TUNEL staining. Western-blot
was used to detect p-STAT3 and p-Akt levels after reperfusion.
Results: There was more myocardial apoptosis at 24h vs 2h after reperfusion in all groups.
PostC significantly reduced myocardial apoptosis and elevated Bcl-2 levels at both 2 and 24
hours after reperfusion. PostC increased p-STAT3 and p-Akt levels after reperfusion.
Administration of AG490 reduced p-STAT3 and p-Akt levels and attenuated the
anti-apoptotic effect of PostC. Wortmannin also reduced p-Akt levels and attenuated the
anti-apoptotic effect of PostC but had no effect on p-STAT3 levels. AG490 abrogated the
up-regulation of Bcl-2 by PostC.
Conclusion: PostC may reduce myocardial apoptosis during prolonged reperfusion via a JAK2-STAT3-Bcl-2 pathway. As a downstream target of JAK2 signaling, activation of
PI3K/Akt pathway may be necessary in the protection of PostC. - 中文關鍵字: --
- 英文關鍵字: Ischemia/reperfusion injury; apoptosis; postconditioning; JAK2-STAT3 pathway; Bcl-2.