Protective effects of combination of Xuesaitong and aspirin on cerebral ischemia and reperfusion injury in rats

Objective：To investigate the protective effects of the combination of Xuesaitong（XST）and aspirin on cerebral ischemia and reperfusion injury（CIRI）in rats,and further explore the underlying mechanisms.Methods：A total of 150 male Sprague-Dawley（SD）rats were randomly divided into five groups with 30rats in each group：sham group,middle cerebral artery occlusion/reperfusion（MCAO/R）model group,XST group,aspirin group,and XST＋aspirin group.Rats were pretreated with XST,aspirin,or XST＋aspirin for7 d.One hour after the last administration,a model of CIRI was induced by MCAO/R.Neurological deficits were assessed using Longa’s five-point scale.Cerebral edema was detected by the measurement of brain water content.The volume of cerebral infarction was determined by 2,3,5-triphenyltetrazolium chloride（TTC）staining.The activities of superoxide dismutase（SOD）,catalase（CAT）,and glutathione peroxidase（GSH-Px）,as well as levels of malonaldehyde（MDA）were detected by commercial kits.Enzyme-linked immunosorbent assay（ELISA）was used to determine the levels of interleukin-1（）,interleukin-4（IL-4）,interleukin-6（IL-6）,interleukin-10（IL-10）,tumor necrosis factor-alphamonocyte chemotactic protein 1（MCP-1）,and kynurenine in serum,cerebral cortex,and hippocampus of MCAO/R rats.The protein expression of nuclear factor erythroid 2-related factor（Nrf2）,heme oxygenase-1（HO-1）,I-kappa B alpha（IκBα）,and nuclear factor kappa B（B）/p65 in the cortex were analyzed by western blotting.Results：Treatment of XST,aspirin,and XST＋aspirin significantly alleviated the neurological deficits,cerebral edema,and cerebral infarct volume induced by MCAO/R.Treatment of XST,aspirin,and XST＋aspirin also reduced MDA,,MCP-1,and kynurenine levels,and increased SOD,CAT,GSH-Px,IL-4,and IL-10 levels in serum,cerebral cortex,and hippocampus of MCAO/R rats.Furthermore,treatment of XST,aspirin,and XST＋aspirin decreased the expression of nuclearB/p65 and increased the expression of IκBα,nuclear Nrf2,and HO-1.Importantly,the combination of XST and aspirin enhanced the protective effects of XST or aspirin treatment alone on CIRI in rats.Conclusion：The combination of XST and aspirin significantly inhibited oxidative stress and inflammation in serum,cerebral cortex,and hippocampus of MCAO/R rats.The combination of XST and aspirin exerted more protective effects than XST or aspirin treatment alone.The combination of XST and aspirin might provide the synergistic therapeutic effects on CIRI,and deserve further clinical investigation.

Combination of Shuxuetong and aspirin protects against cerebral ischemia/reperfusion injury through ameliorating coagulation and fibrinolysis system

Objective：To explore the influence of the combination of Shuxuetong（SXT）and aspirin on coagulation and fibrinolytic system of rats.Methods：Suture method was applied to establish focal cerebral ischemia-reperfusion injury models in rats.SD rats were randomly divided into sham group,middle cerebral artery occlusion/reperfusion（MCAO/R）group,aspirin group,SXT group,and SXT＋aspirin group（S＆A）.The neurological deficits were assessed according to Longa’s grade 5 scoring method.The cerebral edema was detected by measuring the content of water in brain tissue.The volume of cerebral infarction was observed by 2,3,5-Triphenyltetrazolium chloride（TTC）staining.Blood plasma was collected by abdominal aortic method to test maximum platelet aggregation rate and four blood coagulation.CD61,CD62p,6-keto prostaglandin F1αantithrombinⅢ（AT-Ⅲ）,D-dimer,plasminogen activator inhibitor-1（PAI-1）,tissue factor（TF）,tissue plasminogen activator（t-PA）,platelet thromboxaneand von Willebrand factor（v WF）content in rat plasma were detected by ELISA.Results：SXT combined with aspirin could improve the neurological deficits,alleviate cerebral edema,and decrease the cerebral infarct value.Compared with the sham operation group,fibrinogen（FIB）,6-AT-III,and t-PA in model group were significantly decreased;Compared with the model group,the above-mentioned indexes in SXT and aspirin treatment group were significantly increased.The prothrombin time（PT）,activated partial thromboplastin time（APTT）,thrombin time（TT）,D-dimer,PAI-1,TF,TXB2,and v WF of the model group were significantly increased;The above-mentioned indexes in blood SXT＋aspirin treated group were significantly decreased.There was a significant difference between the combined group and SXT group.The maximum concentration of plateletsin aspirin treated rats was significantly decreased,however,MPAR was reversed in SXT＋aspirin treated group.Conclusion：SXT combined with aspirin can effectively inhibit platelet activation,regulate the maximum concentration of platelets,and improve coagulation function and fibrinolysis system.