کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2817610 | 1159999 | 2012 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: High mobility box 1 mediates neutrophil recruitment in myocardial ischemia–reperfusion injury through toll like receptor 4-related pathway High mobility box 1 mediates neutrophil recruitment in myocardial ischemia–reperfusion injury through toll like receptor 4-related pathway](/preview/png/2817610.png)
This study aimed to explore the role of high mobility box 1 (HMGB1) and its receptor toll like receptor 4 (TLR4) on neutrophils in myocardial ischemia reperfusion (I/R) injury. We constructed TLR4-mutant (C3H/HeJ) and control (C3H/HeN) mouse models of myocardial I/R injury and subjected the mice to 30 min of ischemia and 6 h of reperfusion. Light microscope was used to observe structural changes in the myocardium. HMGB1 levels were measured using quantitative real-time PCR and immunohistochemistry. Neutrophil accumulation, TNF-a expression and IL-8 levels were analyzed via myeloperoxidase (MPO) biochemical studies, quantitative real-time PCR and ELISA, respectively. The results demonstrated that fewer neutrophils infiltrated in the myocardium of TLR4-mutant mice after myocardial I/R and that TLR4 deficiency markedly decreased the ischemic injury caused by ischemia/reperfusion, and inhibited the expression of HMGB1, TNF-a, and IL-8, all of which were up-regulated by ischemia/reperfusion. These findings suggest that HMGB1 plays a central role in recruiting neutrophils during myocardial I/R leading to worsened myocardial I/R injury. This recruitment mechanism is possibly due to its inflammatory and chemokine functions based on the TLR4-dependent pathway.
► Fewer neutrophils infiltrated in the myocardium of TLR4-mutant I/R mice.
► HMGB1, TNF-a, and IL-8 levels can be up-regulated by ischemia/reperfusion.
► TLR4 deficincy markedly decreased ischemic injury caused by ischemia/reperfusion.
► TLR4 deficincy inhibited the expression levels of HMGB1, TNF-a,and IL-8 levels.
Journal: Gene - Volume 509, Issue 1, 1 November 2012, Pages 149–153