Research on the protective effect of diazoxide pretreatment on the blood-brain barrier of rats after cerebral ischemia/reperfusion injury / 中国医师杂志

ABSTRACT

Objective To investigate the effect and its mechanism of diazoxide on the blood-brain barrier (BBB) of rats after cerebral ischemia/reperfusion (I/R) injury.Methods Sixty Wistar rats were randomly divided into sham operation group,I/R group,and diazoxide pretreatment groups of low,middle,large dose (5,10,20 mg/kg).The I/R models of rats were performed to undergo middle cerebral artery embolism by thread.BBB permeability was estimated by Evans blue (EB) dyeing,transmission electron microscope (TEM) was used to observe the modification of interendothelial tight junction (TJ) of capillaries.The expression of aquaporin-4 (AQP4) in every rat brain tissues was detected by immunity histochemistry technique.Results (1) Compared to sham operation group,the permeability extent of EB were significantly increased by I/R,which was distinctly attenuated in middle and large dose of diazoxide pretreatment rats,while no obvious changes were found between I/R and low dose groups.(2) TEM showed that TJ of the brain tissue opened after I/R injury and no significant opening of TJ was observed in middle and large dose of diazoxide preconditioning groups.(3) Compared to sham operation group,the expression of AQP4 in the brain tissue of the I/R group was apparently increased (P ＜0.01).Compared to I/R group,the expression of AQP4 was apparently increased in middle and large dose pretreatment groups (P ＜ 0.01),and there were no obvious difference between low dose group and the I/R group.Conclusions Preconditioning of ischemia/reperfusion injury with diazoxide protects the blood-brain barrier,which may due to keep the TJ closed and decrease expression of AQP4 protein.