| BackgroundWith the improvement of people's living standards,the incidence rate of ischemic cerebrovascular diseases is also increasing,which brings huge economic burden to society and families.At present,the treatment methods of ischemic cerebrovascular disease include drug therapy,thrombolytic therapy,interventional therapy,etc.To some extent,these methods have brought great benefits to patients with ischemic cerebrovascular disease,and their prognosis has been greatly improved.Due to the large number of patients,there are still many patients who are unable to obtain satisfactory treatment results.Many factors restrict the outcome of the disease.We have noticed a very important adverse factor-cerebral ischemia-reperfusion injury.That is,after the reperfusion of the ischemic cerebral vessels,will aggravate the brain injury[1].Thrombolysis and interventional therapy can make the occluded cerebrovascular recanalization,and it is inevitable to face the cerebral ischemia-reperfusion injury.Studying related drugs to improve cerebral ischemia-reperfusion injury is expected to improve the prognosis of ischemic cerebrovascular disease.In this experiment,we selected the adenosine A1 receptor agonist cyclohexyl adenosine to pretreat the rat model of cerebral ischemia-reperfusion,observe its protective effect and further explore its pathogenesis.Hypoxia inducible factor-1??HIF-1??can reduce cerebral ischemia-reperfusion injury by regulating the expression of downstream target genes.Glutathione peroxidase 1?GPx1?Cerebral ischemia-reperfusion injury can be alleviated by anti-oxidation.Whether adenosine A1 receptor agonists can exert brain protective effects by up-regulating the expression of HIF-1?and GPx1 proteins is the focus of this experimental study.ObjectiveTo explore the protective effect of adenosine A1 receptor agonist pretreatment on cerebral ischemia-reperfusion injury in rats and its relationship with HIF-1?and Gpx1.MethodsIn this experiment,clean grade SD rats were selected to make the middle cerebral artery occlusion?MCAO?animal model.60 SD rats were randomly divided into 3 groups:sham operation group?Group F?,Cerebral ischemia-reperfusion group?IR group?,adenosine A1 receptor agonist cyclohexyl adenosine pretreatment group?AP group?,20rats in each group.Each group was divided into 2h group,6h group,24h group,and 48h group according to the ischemia-reperfusion time,with 5 rats in each subgroup.Rats in the IR and AP groups were prepared according to the standard MCAO method.Group F rat model without inserting thread,and the rest were the same as those in the IR and AP groups.48-hour group rats in group F,IR group and AP group were examined by HE staining for pathological changes of brain tissue,and head MRI examination was performed to observe the changes of infarcts.Immunohistochemical method was used to detect the expression of HIF-1?and GPx1 protein in brain tissues of rats in groups F,IR,and AP at different time points,and neurological function scores were used to understand the changes of neurological deficit symptoms in rats.Results1.The neurological function score of rats in IR group was higher than that of F group at each time point,and the neurological function score of AP group was lower than that of IR group?P<0.05?.2.48 hours after cerebral ischemia-reperfusion,the pathological results of rat brain tissue showed that the brain cell damage in the AP group was significantly reduced compared with the IR group,and the brain cells in the F group were normal.3.48 hours after cerebral ischemia-reperfusion,the brain MRI of rats showed that the volume of ischemic focus in the AP group was significantly smaller than that in the IR group,and there was no ischemic focus in the F group.4.With the prolongation of ischemia-reperfusion time,the expression of HIF-1?protein in the IR and AP groups showed a consistent trend:it continued to increase from 2h to 24h and reached a peak,and began to decline at 48h.The expression of HIF-1?protein in AP group was higher than that in IR group?P<0.05?.5.The expression of GPx1 protein in the IR and AP groups gradually decreased from2 hours after cerebral ischemia and reperfusion,to 24 hours to a minimum,and increased at 48 hours,and the expression of the GPx1 protein in the AP group was higher than that of the IR group?P<0.05?.ConclusionThe pretreatment of adenosine A1 receptor agonist cyclohexyl adenosine has neuroprotective effect on cerebral ischemia-reperfusion injury in rats,The up-regulation of HIF-1?and Gpx1 protein is the molecular mechanism of the brain protective effect of adenosine A1 receptor agonist. |
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