栝楼桂枝汤调控NOX减轻脑缺血再灌注大鼠氧化应激损伤的机制研究OA

Objective:To explore the mechanism by which Gualou Guizhi Decoction(GLGZD)mitigates oxidative stress injury in rats with cerebral ischemia-reperfusion by regulating NADPH oxidase(NOX).Methods:Sixty male Sprague-Dawley(SD)rats were randomly assigned to sham operation group,model group,and GLGZD group using a random number table,with 20 rats in each group.In the sham operation group,only the subcutaneous tissue and muscles were bluntly dissected to expose the common carotid artery,external carotid artery,and internal carotid artery,without filament insertion.The model and GLGZD groups underwent middle cerebral artery occlusion(MCAO)modeling.After successful modeling,the GLGZD group received intragastric administration of GL-GZD at a dose of 7.08 mL/kg per day for 7 consecutive days,while the sham operation group and model group were received an equal volume of normal saline via intragastric administration once daily for 7 days.Magnetic resonance imaging(MRI)was used to assess cerebral infarction volume;hematoxylin and eosin(HE)staining was employed to examine pathological changes in brain tissue;and spectrophotometry was utilized to measure NOX activity levels.Additionally,quantitative polymerase chain reaction(qPCR)and Western blot analyses were performed to detect the mRNA transcription levels and protein expression of NOX1 and NOX2.The activi-ty level of Caspase-3 was measured using a Caspase-3 activity assay kit.Results:MRI results indicated no ischemic infarction area in the sham operation group,while a large infarction area was detected in the ischemic hemisphere of the model group.The infarc-tion volume in the ischemic brain tissue of the GLGZD group was significantly diminished compared to that in the model group(P<0.05).Pathomorphological observation revealed intact brain tissue structure and normal neuronal morphology in the sham operation group.In contrast,the ischemic hemisphere of the model group presented significant structural damage,disordered neuronal ar-rangement,nuclear pyknosis,accompanied by extensive apoptosis and necrosis.Furthermore,compared with the sham operation group,the NOX activity in the brain tissue of the model group increased significantly(P<0.05).The mRNA transcription levels and protein expression of NOX1 and NOX2 were significantly up-regulated(P<0.05),and the activity of the apoptosis-related protein Cas-pase-3 was also significantly elevated(P<0.05).Compared with the model group,brain tissue in the GLGZD group showed signifi-cantly alleviated pathological injury and reduced cellular necrosis.The NOX activity,mRNA transcription and protein expression levels of NOX1 and NOX2,as well as Caspase-3 activity,were all significantly lower in the GLGZD group than in the model group(P<0.05).Conclusion:GLGZD may inhibit neuronal apoptosis and alleviate nerve tissue injury by modulating the NOX-mediated oxidative stress response subsequent to cerebral ischemia-reperfusion.