Exploration of the effect of inhibitor of matrix metalloproteinase-9 on blood brain barrier in cardiopulmonary resuscitation in rats

Abstract

To explore the effect of inhibitor of matrix metalloproteinase-9 (MMP-9, SB-3CT) on blood brain barrier (BBB) after cardiopulmonary resuscitation (CPR) in rats. Rats were randomly divided into three groups: the sham-operated group, the resuscitation control group, and the resuscitation treatment group. Cardiac arrest was produced by clamping the endotracheal intubation, and CPR was executed 1 minute later. In the resuscitation treatment group, SB-3CT (25 mg/kg) was injected intraperitoneally after the restoration of spontaneous circulation (ROSC). The rats were executed immediately, and 0, 3, 9, 24 and 48 hours after the treatment. BBB was examined, and the expression of MMP-9 protein and MMP-9 mRNA in brain tissue were detected, and the ultrastructure of brain tissue was studied with electron microscopy. In the sham-operated group, the water content, Evans blue content, MMP-9 protein, and MMP-9 mRNA did not change significantly, and there was no obvious change in microstructure of brain tissue. The expression of MMP-9 protein and MMP-9 mRNA in the resuscitation control group were obviously up-regulated at 3 hours after CPR, peaking at 24 hours. There was also significant change in BBB. The differences were significant statistically compared with sham-operated group. The changes in the resuscitation treatment group were similar to the resuscitation control group, but the levels were lower than those of the resuscitation control group (P<0.05 or P<0.01). The specific inhibitor of MMP-9 (SB-3CT) could decreased the expression of MMP-9, the injury of BBB, and cerebral edema in the cerebral ischemia model with CPR rats, and the protection of cerebral ischemia/reperfusion (I/R) injury after CPR is obvious.