The Effects Of Naoxintong On The Brain Edema After Cerebral Ischemic Reperfusion In Rats

Background and Purpose:Ischemic cerebrovascular disease(ICVD) is one of the frequently occurring illnesses in the nervous system, whose incidence and mortality are so high that it often puts a considerable burden on the patient's family and our society. At present clinical treatment of ischemic cerebolvascular diseases at very early stage with thrombolytic medication has brought hope to patients with cerebral infarction, but also brought lesion due to reperfusion. Reperfusion lesion is related to many pathophysiological mechanisms, of which brain edema is an important pathophysiological mechanism. Studies indicate that aguaporin-4 (AQP4) and matrix mentalloproteinases-9 (MMP-9) have close correlation with brain edema after cerebral ischemic reperfusion.Naoxintong capsule has been in clinical application for many years and is an effective medication in the prevention and treatment of cerebral apoplexy. In this experiment, we used the suture emboli method to establish a rat focal model of middle cerebral artery occlusion, applied naoxintong to interfere, observed the change in cerebral tissue, brain water content and cellular number about positive expressions of AQP-4 and MMP-9 and their relation, and tried to find out the effects of naoxintong on the brain edema after cerebral ischemic reperfusion in rats.Materials and methods:(1) One hundred and forty-four SD rats weighing 250-300 grams were randomly divided into 3 groups: false operation group, ischemic reperfusion group and naoxintong therapy group. The false operation group was again randomly divided into 4 time points: 24h, 48h, 72h and 96h postoperatively. The ischemic reperfusion group and naoxintong therapy group were again divided into 4 times points: 24h, 48h, 72h and 96h. There were 12 rats in each time point.(2) In false operation group, operation was performed, but embolic thread was only inserted into external carotid. In other 2 groups suture embolic method was adopted to establish a rat focal cerebral ischemic reperfusion injury model with ischemic time of 2 hours. At corresponding time point, rats ware killed and their brains were taken out. In each group 6 rats' brain water content was taken out and weighed, and the other 6 rats' brain tissues were made into paraffin blocks.(3) In each rat group administration of medication by gavage was used. From preoperative 3 days to postoperative each time point, gavage was administered twice a day—morning and evening. Each gavage volume was 10ml/kg. In naoxintong therapy group, its suspension was given and the administration volume was calculated by 400mg/(kg·d) naoxintong capsule powder. In false operation group and ischemic reperfusion group only physiological saline was provided.(4)In this experiment all the results were statistically analyzed by SPSS10.0. All data were expressed by Mean±standard deviation(X±S). Multi-average number comparison was analyzed by the variance of two factors, the comparison between 2 and 2 was tested with LSD, and correlative analysis was used with linear correlative analytic method. All was tested by the standard a =0.05 as difference, which is of statistical significance.Results:1. In false operation group, rat brain specimens show no obvious abnormality in cerebral tissue structure under light microscope. In ischemic reperfusion group they show fewer normal nervous cells, more deformed neuron bubbles with pyknotic nucleus and considerable imflamed cell infiltration. In naoxintong therapy group they show less number of deformed neuron bubbles and fewer infiltrated imflamed cells.2. In ischemic reperfusion group and naoxintong therapy group brain water content and the number of positive cells increase obviously at 24h of ischemic reperfusion, reach peak at 48h (compared with other time points P<0.05), remain higher at 72h-96h, and every time point in these two groups has significant difference relatively compared with that in false operation group. Compared with those in ischemic reperfusion group, the brain water content and the number of positive cells of AQP4 and MMP-9 in naoxintong therapy group are lower and are of significance statistically.3. After ischemic reperfusion, the expressions of AQP4 and MMP-9 and the change of brain water content among the 3 groups indicate phasic positive correlation.Conclusion:1. After cerebral ischemic reperfusion, rat brain water content and the positive cell number of AQP4 and MMP-9 increase clearly at 24h of ischemic reperfusion, reach peak at 48h and maintain in higher level at 72h-96h and they three show phasic positive correlation .2. Compared with those in ischemic reperfusion group, the rat brain water content and the number of positive cells of AQP4 and MMP-9 in naoxintong therapy group are lower and indicating that naoxintong can reduce brain edema in rats after cerebral ischemic reperfusion.