The Study On The Effect Of Oxiracetam In Subarachnoid Hemorrhage Treatment

Subarachnoid hemorrhage (SAH) refers to sudden rupture of cerebral vascular due to various reasons. It is a common name that blood flows into subarachnoid, which is divided into spontaneous and traumatic, of which70%-80%of the disease belongs to surgical areas. SAH is not a disease, but clinical symptoms of some diseases. Secondary to cerebral vasospasm after SAH occur in approximately70%. While the secondary vasospasm occur, mortality than2weeks after SAH vasospasm increase1.5-3times. Imaging has showed cerebral artery stenosis. The distal of stenotic artery has reduced perfusion, the patients have corresponding performance of ischemic. Nerve cells to maintain normal function after SAH reduce apoptosis relying on reserve in the cerebral circulation, cerebral metabolic reserve capacity. For the moment. nimodipine (anti-vasospasm) and3H treatment is used to reduce mortality; How to improve nerve cell metabolism as an adjuvant treatment to reduce nerve cell necrosis and apoptosis is still lack of research reports. Oxiracetam(ORC)chemical name4-Hydroxy-2-oxo-1-pyrrolidineacetamide is a new cyclic derivative of GABOB. Which could promote learning, enhance memory,protect damaged nerve cells of the central nervous system and selectively act on the cerebral cortex and hippocampus in the protection or extension of the function of nerve cells to restore. Over the past decade, at home and abroad, oxiracetam, which has been used to treat various pathological traumatic brain injury, hypoxia and chronic brain dysfunction has achieved good results. It is confirmed that ORC has pharmacological effects on the nerve cells. The mechanism demonstrated includes the following aspects:ORC has a stimulating effect on specific central nervous pathways by penetrating the blood-brain barrier;effectively improve the ability of brain oxygen utilization;promote the synthesis of phosphatidylcholine and phosphatidylserine acetamide;activate adenylate kinase, to increase ATP synthesis and improve ATP conversion (ie, glucose metabolic rate); activate glycolysis, to increase glucose utilization, promote the energy metabolism of brain cells, increase brain ATP formation and transfer, and improve the brain cells of ATP/ADP ratio in case of cerebral ischemia; Reduce cerebral vascular resistance, inhibit platelet aggregation, improve microcirculation, increase blood flow of brain tissue; promote damaged nerve cell to plasticity repair; reduce neurotoxicity of excitatory amino acid. Clinically ORC is used as a cerebral protective agent in the treatment of subarachnoid hemorrhage (SAH) to improve the prognosis. A number of studies indicate that the inhibition of apoptosis will be able to play a cerebral protective effect.This research aims to observe the hippocampal neuronal apoptosis by establishing SAH model of rats, and explore the impact of oxiracetam on neuronal apoptosis, to provide a theoretical basis for brain lesions after Apoptosis is the occurrence of programmed cell death induced by the intracellular and specific physiological or pathological factors. The present study shows that genes within cells that controls the occurrence and development of apoptosis.External factors affect the expression of these genes through signal transduction or activation of its expression product, thereby indirectly regulating apoptosis.There are many studies on the mechanism of apoptosis many different types of cells at different growth stages have different apoptotic pathways, but this difference vary widely mainly with the molecular mechanisms of early induced apoptosis, but once apoptosis start early apoptosis signal will be pooled into a common execution path, causing the cells to produce a similar characteristic morphological and biochemical changes.The current study showed that caspase-3is the important one of the Caspase family, confirmed in the downstream of apoptotic execution pathway, is common downstream effector part of apoptotic pathway. Caspase-3could directly or indirectly enzymoolysis a series of protein required for survival, causing apoptosis. Bcl-2family is an important inhibitor of apoptosis gene in the inhibition of neurocytes’apoptosis, Bcl-2protein, directly affect the permeability of mitochondrial outer membrane to prevent the apoptosis signals’transduction by reducing the concentration of the cell and the nucleus of Bax. Bax is a major pro-apoptotic gene and its apoptosis induction mechanism is accomplished through the formation of Bax homodimers, Bcl-2protein inhibits apoptosis by forming a heterodimer with Bax. Bcl-2/Bax is a relatively balanced system, the overexpression of Bax accelerated apoptosis rate; the overexpression of Bcl-2decelerated apoptosis rate. Bcl-2/Bax ratio determines whether apoptosis occur or not. The mechanism confirmed is Bax are involved in the structural changes of the mitochondrial membrane, and correlation with the release of the Cyte-c.With the stimulation of apoptotic factors, the release and distribution of Cyte-c is regulated by Bax and other factors. Cyte-c released into the cytoplasm lead to induce apoptosis the help of ATP or dATP.[Methods] Choose35male Wistar rats, establish a rat model of SAH by Cisterna magna injection with autologousfresh femoral arteryl blood, rats were randomly assigned to the blank control group, saline control group SAH group, the oxiracetam injection in the treatment group1and oxiracetam injection in the treatment group2(n=7), these groups were killed after14days, Real-Time PCR detected the changes of Bax, Caspase-3and anti-apoptotic factor Bcl-2in the hippocampus nerve tissue in each group, and further by Western blot to verify this change[Results] Caspase-3and Bax expression in the hippocampus are significantly increased in SAH group as compared to control (P<0.05). Bcl-2expression is also increased in SAH group (P<0.01). Caspase-3expression are significantly decreased in the oxiracetam treatment group1and2comparing with control groups (P<0.01), and Bax expression was significantly decreased in oxiracetam treatment group as compared with SAH group (P<0.01). However the changes of Bcl-2expression are not statistically different among groups (P>0.05).[Conclusion]1.This study domonstrates that SAH could induce cell apoptosis.2.This study also shows oxiracetam could inhibit cell apoptosis, and has dose-related effect of anti-apoptosis. These results suggest oxiracetam might excert neural protective effect on SAH patients by inhibing cell apoptosis, and improve oxygen saturation, energy utilization, and cell metablism.