| Subarachnoid hemorrhage,subarachnoid hemorrhage,SAH)is a serious threat to human life and health of cerebrovascular disease,with the development of neurosurgery and imaging techniques,more can be cured with surgery or interventional therapy,but SAH with brain damage can kill 17%?49%of the patients or disabled,is the key link to ruptured aneurysm treatment curative effect and research hot spot.Subarachnoid hemorrhage in patients with cerebral blood flow decreased,cerebral ischemia and oxygen using down even the performance of local cerebral infarction,intracranial vascular spasm was thought to be caused of the main causes of ischemic brain injury after subarachnoid hemorrhage,but prospective clinical study suggests improving vasospasm did not significantly improve the clinical prognosis of patients with subarachnoid hemorrhage,which prompted the ischemic brain injury after subarachnoid hemorrhage major vascular bed may not be a large blood vessels and is probably the microcirculation.In recent years a large number of studies have shown that after subarachnoid hemorrhage sulfonyl urea receptor 1(Sulfonylurea receptor 1,Sur 1)related to the Transient receptor potential of melatonin four(Transient receptor potential melastatin 4,Trpm4)channel to express a large increase,it through enhanced excitability toxicity,endothelial cell necrosis and inflammation,thrombus and so on the many kinds of ways to increase microvascular spasm,cause microcirculation dysfunction.Sulfonylurea glyburide has been used for more than 40 years to reduce hypoglycemia by inhibiting katp-related surl-kir6.2 pathway in islet of insulin cells.In the past 5 years,animal pathological studies and clinical trials of ischemic stroke have confirmed that glibenide can inhibit the expression of surl-trpm4 channel,thereby reducing infarct volume,neuron apoptosis and bleeding transformation,and thus play a multi-effect protective role.In this study,the changes of cerebral microcirculation and sensory cortical blood flow response after glibenide treatment of subarachnoid hemorrhage were studied by means of laser speckle imaging.The experiment is composed of two parts.Part ?:Study on microcirculation of cerebral cortex and the changes of blood flow response of sensory cortex under somatosensory stimulation after subarachnoid hemorrhage in miceObjective:To preliminarily verify the association between ischemic brain injury and cerebral microcirculation after subarachnoid hemorrhage by means of laser speckle imaging,and to provide data support for the evaluation of efficacy of glibenide in the treatment of subarachnoid hemorrhage.Methods:the experiment was divided into the normal control group,the saline group and the SAH group.The skull of the right sensory cortex area of the mouse was carefully polished to translucent,forming a transparent skull observation window of about 2×2 square millimeters.The subarachnoid hemorrhage model was constructed by injecting blood into the anterior cistum of the optic chiasm,and the neurological function of the mice was scored by Garcia scale.The laser speckle imaging technique was used to collect the resting blood flow data of the sensory cortex and the blood flow response data under the electric stimulation of the front PAWS.The correlation between the flow velocity and the area under the response curve of the sensory cortex and the neural function was analyzed.Results:the neurological function score of SAH group was lower than that of saline group(p<0.05).The decrease of sensory cortical blood flow velocity in SAH group was statistically different from that in saline group(p<0.05).In each group,the limited blood flow in the observed somatosensory functional area increased with time after electric stimulation of the forepaw.The change amplitude of blood flow response in SAH group was smaller than that in saline group(p<0.05).The peak time delay of SAH response was statistically different from that of saline group(p<0.05).The area under the SAH blood flow response curve was smaller than that under the saline group(p<0.05).The blood flow velocity of the sensory cortex after subarachnoid hemorrhage was positively correlated with the neurological function score(r=0.9173,p<0.0001).The area of sensory cortical blood flow under somatosensitive stimulation after subarachnoid hemorrhage was positively correlated with the neurological function score(r=0.5951,p<0.05).Conclusion:the disturbance of microcirculation in the sensory cortex after subarachnoid hemorrhage is closely related to the degree of neurological impairment.Part ?:The study of microcirculation and blood flow response under functional activation in the cerebral cortex of mice treated with glibenclamide after subarachnoid hemorrhageExperimental study ?:The experimental study of glibenclamide efficacy evaluationObjective:to investigate whether glyburide can improve cerebral cortical microcirculation and blood flow response under functional activation after subarachnoid hemorrhage.Methods:the experiment was divided into media group and glibenclamide group,and treated by intraperitoneal injection of 25ug/kg.The Garcia scale scored the neurological function of the mice.The data of sensory cortical blood flow velocity and sensory cortical blood flow response under somatosensory stimulation were collected by laser speckle imaging in the media group and glibenclamide group respectively.Results:the score of nerve function in glibenide group was higher than that in media group(p<0.05).Glyburide group of the sensory cortex blood flow speed is faster than the media have statistical difference(p<0.05),the glyburide group more variations in the sensory cortex blood flow responses of statistically significant in the saline group(p<0.05),blood flow responses of peak time was statistically difference in the saline group(p<0.05),blood flow response area under curve more statistically significant in the saline group(p<0.05).Conclusion:glibenide can improve neural function score by improving cerebral cortex microcirculation and blood flow response under functional activation.Experimental study 2.Experimental study of glyburide dosageObjective:To investigate the dose-dependent effect of glibenide on the microcirculation of sensory cortex after subarachnoid hemorrhage in mice.Methods:the experiment was divided into single dose groups and multiple dosing,single drug groups within 5 minutes after SAH model induced by 25 ug/kg dose of abdominal cavity to medicine,many times to medicine group after SAH model induced by 5 minutes,12 h,24 h with 25 ug/kg respectively the dose of the abdominal cavity,two groups,respectively,in 48 h after modeling neural function and sensory cortex microcirculation data collection.Results:there was no significant difference in neurological function score between the multiple administration group and the single administration group(p>,0.05).There was no significant difference in sensory cortical blood flow velocity between the multiple administration group and the single administration group(p>,0.05).Multiple dosing of sensory cortex blood flow response amplitude and single drug group no statistical difference(p>0.05),multiple dosing of sensory cortex blood flow response tmax and single drug group no statistical difference(p>0.05),multiple dosing of sensory cortex blood flow response area under the curve with a single dose group no statistical difference(p>0.05).Conclusion:The efficacy of glibenclamide after subarachnoid hemorrhage has no significant correlation with dose. |
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