| background Subarachnoid Hemorrhage is a general clinical neurosurgical emergency,and the proportion of its incidence in acute cerebrovascular diseases is increasing year by year.Among the many diseases leading to arachnoid hemorrhage,especially spontaneous arachnoid hemorrhage is the most common,and the most common cause is intracranial aneurysm rupture,accounting for about 80%.With the development of medical science and technology and the accumulation of clinical experience,although early clipping or interventional embolization of aneurysms can save the life of patients in time and avoid the risk of re-rupture of aneurysms,it can significantly reduce the mortality rate,but craniotomy clipping or interventional embolization of aneurysms can not simply stop the pathophysiological process of intracranial brain tissue cells after subarachnoid hemorrhage.After subarachnoid hemorrhage,brain tissue cell damage still exists and continues to progress,eventually leading to poor prognosis.In the past,cerebral vasospasm has been considered to be one of the main factors causing complications after SAH surgery and leading to high disability rate or high mortality after discharge from the hospital.Secondary brain injury caused by cerebral vasospasm is considered to be one of the main causes of early brain tissue cell injury,and it is also the intensification of brain cell edema,free radical production,cell apoptosis and autophagy in early brain tissue after SAH,which are considered to be highly related to the poor prognosis of the disease.Therefore,it is particularly important to explore the therapeutic methods that can relieve vasospasm after subarachnoid hemorrhage,reduce brain tissue cell edema,remove free radicals,inhibit and improve apoptosis.At present,it is believed that AKT is a key factor in the important anti-apoptotic pathway.After the activation of PI3K/AKT channel,Bad,Caspase-9,NF-B and other factors can inhibit the mitochondrial apoptosis pathway,and at the same time,it can activate Ikk to regulate the transcription of anti-apoptotic genes.After neuronal injury,a large amount of caspase-3 is activated by anti-inhibition of AKT activity and catabolism of AKT.AKT loss of activity leads to the progression of apoptosis.Caspase-3 has been shown to inhibit and degrade AKT,which antagonizes the anti-apoptotic effect of AKT.Melatonin,as an endogenous hormone secreted by the pineal gland,has the functions of scavenging free radicals and activating antioxidants.At the same time,endogenous steroids have the characteristics of free passage through the blood-brain barrier.However,the effect of melatonin alone on antiedema and free radical scavenging of brain tissue cells after DBI is limited.Edaravone,as a free radical scavenger,has been confirmed in previous experiments.It can increase the activity of SOD in damaged brain cells of rats,inhibit the over-expression of MDA and MOD,and achieve the inhibition of nerve cells Therefore,it is particularly important to explore the method of combined application of melatonin and edaravone,which is expected to achieve the synergistic effect of 1+1>2 in clinical application.Method A total of 80 healthy adult SD rats were selected according to the regulations.The rats were divided into sham group,placebo group,edaravone group(EDA),melatonin group(MEL)and melatonin combined with edaravone group(MEL+EDA).The neurological deficit scores of SD rats were observed at 24 hours,48 hours and 72 hours after injection of autologous tail blood through the occipital cidal,and at 24 hours of the experiment At the end of the experiment,some of the rats were sacrificed by decapiting,part of the brain tissue was separated and dried,and the brain water content was measured.After 72 hours,the remaining brain tissue was used for immune ohisto chemical staining to observe the expression of positive cells after SAH in each experimental group.At the same time,Western blot was used to detect the protein expression of PI3 K,AKT and Caspase-3 in the injured brain tissue.Results 1.Melatonin combined with edaravone is more effective than edaravone or melatonin alone in improving the recovery of neurological function after subarachnoid hemorrhage(SAH)in SD rats.2.In the experimental model of subarachnoid hemorrhage(SAH)in SD rats,melatonin combined with edaravone can further enhance the ability of inhibiting brain tissue edema compared with edaravone or melatonin alone after SAH.3.In the experimental model of subarachnoid hemorrhage(SAH)in the early brain tissue injury,melatonin combined with edaravone compared with edaravone or melatonin alone activated the PI3K/AKT signaling pathway,and the activation of anti-apoptotic proteins was further deepened.4.In the experimental model of subarachnoid hemorrhage(SAH)in SD rats,melatonin combined with edaravone was more effective than edaravone or melatonin alone in inhibiting the expression of Caspase-3 apoptosis protein in the injured brain tissue of SD rats.Conclusions 1.Melatonin combined with edaravone has a synergistic effect on improving the recovery of neurological function in SD rats with SAH in EBI.2.Melatonin combined with edaravone has a synergistic effect on inhibiting brain tissue edema compared with edaravone or melatonin alone in the early stage of brain tissue injury after subarachnoid hemorrhage(SAH)in SD rats.3.In the experimental model of subarachnoid hemorrhage(SAH)in SD rats,melatonin combined with edaravone has synergistic advantages over edaravone or melatonin alone in activating PI3K/AKT signaling pathway and increasing the expression of anti-apoptotic proteins.4.Melatonin combined with edaravone has a synergistic effect in inhibiting the expression of Caspase-3 apoptosis protein compared with edaravone or melatonin alone in the early brain tissue injury after SAH in SD rats. |
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