Effects And Its Mechanisms For NOT Intervention To Treat CIRI Rats

Background Cerebrovascular disease is a kind of disease which refers to the brain tissue damage caused by the brain blood circulation obstacle. CVD including two categories,ischemic form and hemorrhagic form. Cerebrovascular disease has high incidence and high mortality. According to the data, about 15 million people died of this disease each year around the world, became the first cause of death. Ischemic cerebrovascular diseaseappear means to brain tissue necrosis caused by oxygen deficit. The effective method is reperfusion to restore the blood flow of ischemic area. However, patients after infusion, brain tissue did not realize the functional recovery, further aggravating instead, this is the so-called cerebral ischemia-reperfusion injury. The pathological process and the mechanism of CIRI is very complex, this process is a rapid cascade involving multiple links, including the activation of apoptosis gene, the release of excitatory amino acids, intracellular calcium ion balance, energy metabolic disorders, and oxide free radical generation. These links contact each other closely to form a vicious cycle, eventually led to the brain tissue necrosis or apoptosis. There are significant research progress on the complex pathophysiology of CIRI, but effective treatment remains limited, many people researches on drug treatment. An idea is using the thrombolytic drugs, such as recombinant tissue plasminogen activator, but it can easily lead to cause the risk of bleeding and aggravate the damage. Another idea is using nerve protective agent, finding the targets in the key links of CIRI to block, In order to effectively reduce cerebellar infarction volume and improve nerve function, but this kind of protective agent has not been found yet after many experiments.Normobaric oxygen therapy is also known as atmospheric pressure high concentration oxygen therapy, which refers to make the patients wearing oxygen mask breathing high concentrations of oxygen therapy tin the case of no pressure. In recent years, many studies have found that it can significantly reduce the model mouse tissue infarction volume and relieve cerebral edema and inflammatory reaction in treatment of acute ischemia-reperfusion injury for rats model by using NOT, which can be used to rescue acute ischemic tissue. But whether NOT can really protect acute ischemia-reperfusion injury of brain tissue effectively, its specific mechanism is the problem to be solved and need to be further more in-depth research.Objectives To treat acute ischemia-reperfusion injury rats model By using NOT. To explore the protection and its possible mechanism of NOT to treat CIRI rats model from behavioral level and molecular level, providing the basis for looking for effective method for treatment of CIRI.Methods Five control model and 10 CIRI rats models made by middle cerebral artery occlusion method, neurologic deficit score is using for rats to evaluate the models is successful.70 healthy male SD rats were randomly divided into control group, model group, cerebral ischemia-reperfusion NOT 3h group,6h group,9h group,12 h group and 24 h group. Control group was only carried out on the common carotid artery and external carotid artery ligation, line switch of CIRI model group were pulled out to use reperfusion for 24 h after ischemic for 1.5 h, the rest of groups were placed in the homemade high airtight device respectively for NOT processing 3 h,6 h,9 h,12 h,24 h; 24h after reperfusion, neurologic deficit score was detected for all groups, the brain tissue were separated and infarction volume were determined; Activity of SOD and MDA were tested for each rat brain tissue homogenate; Changes of TNF-aand IL-β1 in the model rats brain tissue at both transcription level and translation level were detected by using real-time fluorescent quantitative PCR, enzyme-linked immunoas- say and Western blot method.Results1、Five rats of control group were scored zero points. Ten rats of model group were showed Symptoms such as forepaws could not fully extended, dumping to the contralateral et.al, and the score was significant different compared with control group (P= 0.000), showed that the rats model is building successfully.2Ten rats of control group scored zero points, compared with control group, scores of other groups were increased significantly (P< 0.05), compared with model group, NOT 3 h and 6 h group scores were significantly decreased (P< 0.05), the difference is statistically significant.3、In addition to the control group, the rest groups all have different degree of cerebral infarction, have different degree, compared with model group, NOT 3 h,6 h group and cerebral infarction volume 9 h group decreased significantly (P< 0.05) and significant difference, NOT 12 h and 24 h group no obvious difference compared with model group (P> 0.05).4、Compared with the control group, the rest of the groups of brain tissue SOD activity significantly decreased, MDA content increased significantly (P< 0.05), compared with model group, NOT 3 h and 6 h group significantly increased SOD activity and MDA content decreased significantly (P< 0.05).5、Compared with the control group, the rest of the group of TNF alpha and IL-beta 1 transcription level increased significantly (P< 0.05), compared with model group, NOT 3 h,6 h group with 9 h two inflammation, there is a downturn in the transcription factor which NOT the most significant the 6 h group (P< 0.05).6、ELISA and WB test showed that TNF alpha and IL-beta 1 protein expression levels of each group were higher than control group (P< 0.05), compared with model group, two of the inflammation factors in NOT 3 h group were decreased most significantly (P< 0.05).Conclusion NOT has protection effects on acute CIRI rats. It is very important for using NOT to treat CIRI in choosing of right time and duration. To carry out reperfusion within 1.5 h, using NOT intervention to treat CIRI 3 to 9 h have showed certain curative effects,3-6 h is the best. The possible mechanism for NOT to treat CIRI may be that, reducing oxidative stress of brain damage zone and decreased the expression of inflammatory factors. Our research will providing the certain basis for clinical treatment of CIRI.