Effects Of Captopril On Blood-brain Barrier Permeability And Matrix Metalloproteinase-9, Matrix Metalloproteinase-2Expression After Cerebral Ischemia Reperfusion In Rats

Objective: Ischemic cerebrovascular disease which is serious harm to humanhealth and life is one of the most common diseases. Prompt reperfusion of ischemicbrain tissue is critical for restoring normal function. Blood-brain barrier (BBB) damageis an important pathophysiological basis of cerebral ischemia reperfusion injury.According to the study, matrix metalloproteinase-9（MMP-9）which is most closelyrelated to the blood-brain barrier damage, degrade the ECM components of thebasement membrane leading to increased permeability of the blood-brain barrier. Inclinic hypertension has long been recognized as one of the most important risk factorsof cerebrovascular disease. Angiotensin converting enzyme inhibitor Captopril is one ofthe antihypertensive drugs in clinical, which is also a member of the matrixmetalloproteinases (MMPs) family. In this experiment, as the foundation of middlecerebral artery occlusion (MCAO) model, we objective to research the effects ofCaptopril on blood-brain barrier permeability and the expression of matrixmetalloproteinase-9and matrix metalloproteinase-2after cerebral ischemia reperfusionin rats and to approach the function and mechanism of Captopril on cerebral ischemiareperfusion injury and to provide a theoretical basis for clinical application ofangiotensin converting enzyme inhibitor drug treatment of hypertension caused byischemic cerebrovascular disease.Methods: We established a middle cerebral artery occlusion model byintraluminal suture method. Ischemia time was2h and reperfusion time was1,3,5,7,9d, respectively. Five rats were divided into five groups at each time point. The ratswere given Captopril50mg/kg daily from the first day after surgery. Cerebralinfarction model was identified by2，3，5-triphenyltetrazolium chloride (TTC) staining.The neurological deficit scores of cerebral ischemia reperfusion injury was evaluated by using the method of Longa5. The BBB permeability was evaluated by measuring thecontent of the extravascular exudation of Evan’s blue (EB). Matrix metalloproteinases-9(MMP-9) and Matrix metalloproteinases-2(MMP-2) activities were assessed by gelatinzymography. We observed the BBB permeability and MMP-9, MMP-2expression afterreperfusion and giving Captopril at each time point, as well as the relationship.Results:1. This study established a middle cerebral artery occlusion model.2. After2h of brain ischemia, TTC staining of ischemic focus tends to be stable,involving most areas of the middle cerebral artery. Cerebral edema was obvious.3. Neurological deficit score was significantly reduced with the growth of thedelivery time after reperfusion.4. After cerebral ischemia reperfusion,the contents of EB was the highest at thefirst day and decreased with administration time increasing, but a slight increase in the7to9days (p <0.05).5. After cerebral ischemia reperfusion, the expression of MMP-9was the highestat the first day and decreased in the3to7days, but a slight increase in the firs7to9days(p <0.05).6. After cerebral ischemia reperfusion, the expression of MMP-2was the highestat the third day and decreased in the3to9days (p <0.05).7. After cerebral ischemia reperfusion, EB content of brain tissue and MMP-9expression has the same temporal trend. The former two time trends and MMP-2expression were not consistent.Conclusions:1. According to neurological deficit score improving significantly, it ishypothesized that Captopril is in favour of nerve function recovery by inhibiting tissuemetalloproteinase.2. Large doses of Captopril in use within7days reduced the permeability of theblood-brain barrier by inhibiting MMP-9activity and play a protective effect oncerebral ischemia reperfusion injury.3. MMP-9activity has actually strengthened and the permeability of theblood-brain barrier also increased after using large doses of Captopril more than7days.It is indicated that using large doses of Captopril may aggravate cerebral ischemia andreperfusion injury after a week.4. After cerebral ischemia reperfusion, the blood-brain barrier permeability presents time-related with the expression of MMP-9, but no time correlation with theexpression of MMP-2. It is suggested that MMP-9is one of the important factorsaffecting the blood-brain barrier.