Protective Effects Of SalB/Rg1 On Acute Ischemic Stroke Of Rats

Background: Ischemic stroke is a central nervous system disease that seriously endangers human life caused by focal occlusion or arterial stenosis in the brain.Ischemic stroke usually results to permanent disability or death,has been the major leading causes of years of life lost in the world.As an enormous public health problem,ischemic stroke imperatively needs for more effective therapies.Blood brain barrier(BBB)injury is an important pathological process leading to hemorrhagic transformation and poor prognosis.We have previously demonstrated that the combination of salvianolic acid B and ginsenoside Rg1(SalB/Rg1)inhibited myocardial hemorrhage and showed significant protective effect on coronary vessels after myocardial ischemia reperfusion.In the present study,we want to evaluate the effects of SalB/Rg1 on BBB integrity and further explore its potency for therapy on ischemic stroke.Methods: In this study,24 h acute ischemic stroke animal model(MCAO)was made by using thread embolism to block the middle cerebral artery in rats.The acute cerebral ischemic reperfusion injury(CI/R)model was established by reperfusion 24 h after the middle cerebral artery was blocked by thread embolism.Longa score and EBST were used to evaluate the motor function of rats after stroke.The infarct size of stroke was evaluated by2,3,5-triphenyltetrazolium chloride staining(TTC).The pathological changes of brain tissue were evaluated by hematoxylin-eosin(HE)staining.Nissl staining was used to evaluate the number of nerve cells.BBB integrity was evaluated by Evans blue staining.The brain edema was evaluated by the ratio of dry to wet weight.Gelatin enzyme profiles and immunohistochemistry were used to investigate the mechanism of SalB/Rg1.Results: In the present study,both MCAO model and CI/R model were set up to evaluate the efficiency of SalB/Rg1.SalB/Rg1 decreased infarct area through TTC stain and improved neurological behavior through Longa Score or Left-Biased Swings on both MCAO rats and CI/R rats.Neural protection of SalB/Rg1 against ischemia or ischemic reperfusion injury was evidenced by inhibition of nucleus pyknosis,liquefaction necrosis through H&E stain and Nissl stain.Furthermore,protection of SalB/Rg1 on BBB was more significant on CI/R rats,accompanying with the down-regulation of matrix metalloproteinase-2(MMP-2)and matrix metalloproteinase-9(MMP-9),and recovery of zonula occludens-1(ZO-1)expression.Conclusions: Collectively,SalB/Rg1,with dual-protection on neuron and cerebral vessels,is a new candidate for acute ischemic stroke.SalB/Rg1 down-regulated the infarct area and improved neurobehavioral deficits in a wide time window including ischemia and reperfusion...