The significance of S100A8 expression to cerebral ischemia reperfusion injury / 中华急诊医学杂志

ABSTRACT

Objective To study the expression of S100A8 and the relationship between S100A8 and Toll-like receptor 4 (TLR4) in focal cerebral ischemia reperfusion (I/R) injury.Methods C3H/HeJ mice with TLR4 gene mutation (n =30) and C3H/HeN with normal TLR4 gene mice (n =30) were divided into 4 groups at random (random number),namely C3H/HeJ model group (n =18),C3H/HeJ control group (n =12),and C3H/HeN model group (n =18).C3H/HeN control group (n =12).Middle cerebral artery was occluded to make I/R model in mice by using thread embolism method.Brain tissues were collected after ischemia for one hour and reperfusion for 12 hours.Stroke outcome was evaluated by determination of infarct volume of brain tissue and assessment of neurological scores.And brain injury after cerebral I/R was observed by optical microscope after TTC and HE staining.The immunofluorescence technique and RT-PCR were used to determine the protein level and expression of S100A8 mRNA in damaged brain tissues.Results Compared with C3H/HeN model mice,TLR4-deficient model mice (C3H/ He J) had lower infarct volumes and better outcomes of neurological function after resuscitation for 12 hours.Compared with control groups,the expression of S100A8 mRNA and level of S100A8 protein increased greatly in damaged brain tissues of model mice after I/R injury.In addition,model mice with lacked TLR4 (C3H/HeJ) had lower expression of I/R-induced S100A8 mRNA than C3H/HeN mice in model group,indicating that the close relationship between the levels of S100A8 and TLR4.Conclusions S100A8 interaction with TLR4 might be involved in brain damage and in inflammation triggered by I/R injury.