The Effect Of Tetramethylpyrazine On Cognitive Function And GABAR Expression Of Rats Under Hypobaric Hypoxia Condition

Objective: To provide reference value for clinical prevention and treatment of hypoxic ischemic brain damage through examining the influence of tetramethylpyrazine for the behavioral science,morphology and the expression of gamma aminobutyric acid(GABA)receptor and forkhead box P2(FOXP2)in hippocampus of rat,eventually to investage the effect of tetramethylpyrazine for hypoxic hypoxia on learning and memory function.Methods: 120 Sprague Dawley rats were randomly divided into low hypoxic hypoxia and high hypoxic hypoxia groups,then according to different time points every group was divided into 1d,3d,7d 15 d,30d group,12 rats per each group.Experiment group and the control group were treated with tetramethylpyrazine and 0.9% normal saline,respectively.The hypoxic hypoxia environment were made by putting the rats in a hypobaric chamber at a simulated altitude of 5500 meters for different days.The capabilities of learning and memory of rats were detected by Morris water maze test.Nissl staining method was used to observe the morphological changes of hippocampal neurons in rats in different groups;Immunohistochemical staining was used to survey the expression of GABAB1 R and FOXP2.The expression of GABA receptor and FOXP2 protein in hippocampus of rat was determined by western blot method.Results: 1)Morris water maze test showed that the total distance of rats in the simulated hypobaric hypoxia control group were longer than that in the tetramethylpyrazine group(P<0.01)and the number of accrossing the bestride platform was increased than that in the hypobaric hypoxia control group(P<0.01)from the third day;2)Nissl staining showed that with the increase of the number of days,the damage degree of hippocampal neurons in rats was more clear in hypoxia control group.The main finding was that the number of Nissl bodies were less and less,edemaoccured in nerve cells,the dividing line between cells was becoming unclear and nucleus was clear to indistinct,however the number of nissl bodies tended to normal,the nucleus was clear,the cells were arranged neatly and edema gradually became normal after TMP intervention;3)Immunohistochemistry method results showed that the expression of GABAB1 R and FOXP2 have no statistical significance in hippocampus of rats in each group(P>0.05);thuogh the expression of GABAB1 R decreased gradually from the third day compared with TMP group(P<0.05)and the expression of FOXP2 decreased from the seventh day compared with TMP group(P<0.05);4)Western blot results showed that the expression of GABAA?1 receptor have no statistical significance(P>0.05);however,GABAB1 receptor and FOXP2 protein rose from the third day(P<0.05);5)The expression of GABAA?1 receptor and FOXP2 protein expression were correlated to total distance of the Morris water mase in the control group(r=-0.738,P<0.05;r=-0.693,P<0.05),and the expression of GABAB1 receptor was correlated with FOXP2 protein level(r=0.834,P<0.05).Conclusion: The simulated high-altitude hypobaric hypoxia can decrease the learning and memory abilities of rats,but tetramethylpyrazine can improve this situation,and these changes might be related to the increase of GABAB1 R receptor and FOXP2 expression in hippocampus of rats.