Study On Neuron Protection Of Batroxobin In Hippocampal CA1 Territory Of Gerbils

Stroke is one of the most threatening diseases for human health. The patients are always afflicted with functional disorder of movement, sense, cognition and self-care in early stage after stroke. If the functional disorder cannot be effectively treated in time, it will influence the quality of life of patients and become a burden to society and their families. Presently, the remedy and rehabilitation therapy constitute the methods which be used for treating the patients after stroke.Thrombolytic therapy is regarded as an effective way to treat ischemic stroke nowadays,but it may accompany hemorrhage.Studies have found that batroxobin does something good in neuroprotection and it has some effect on thrombolysis.Batroxobin could directly affect plasma flbrinogen to form non-bind mono or multiple fibrin which could be easily cleaned by fibrinolysis system,and could promote the t-pA releasing from the endothelial cells ,enhance the effect of t-pA and lower the activity of plasminogen activator inhibitor.It could decline the plasma flbrinogen levels and the blood viscosity.The best dose that batroxobin protects forebrain ischemia-reperfusion injury in experiment hasn't been reported,thus,thebest dose study may give the dose guide to corresponding animal experiment.The results had showed that Bcl-2,eNOS,VEGF and Akt have the role of reducing cell apoptosis.There are many animal experiments about brain protection of batroxobin,but collecting study hasn't been seen.We examine the expressions of Bcl-2,eNOS,VEGF and Akt in different time by intraperitoneally injection,and explain probable mechanism and relationship between time and efficiency of batroxobin to protect brain neurons.Akt is mainly activated by phosphatidylinositide 3'-0H kinase (PI-3K).It has been established that activation of Akt plays an important role in celluar survival by phosphorylating its substrates at serine or threonine residues.Serine-threonine kinase can be completely inhibited by Wortmannin. In this project,we studied the relationship between PI-3K/Akt signaling pathway and hippocampal ischemic injury in gerbils by intracerebroventricular injection.There are four sections in this project: 1. To study the best dose of batroxobin to protect forebrain ischemia in gerbils 2. The changes of ultrastructure in hippocampal pyramidal in cerebral ischemic -reperfusion in gerbils.3. The probable mechanism of batroxobin to protect brain neurons 4.The relationship between PI-3K/Akt signaling pathway and hippocampal ischemic injury in gerbils.The results manifested that 8 BU/Kg, 16BU/Kg and 32 BU/Kg batroxobin dose groups had significantly difference with 1 BU/Kg, 2BU/Kg, 4 BU/Kg and control groups (P<0.01) . The rate of apoptosis cells in the hippocampal CAl territory had a decreasing tendence with the dose increase in 8 BU/Kg ,16BU/Kg and 32 BU/Kg batroxobin dose groups,but there hadn't significantly difference in those dose (P>0.05 ) .It hadn't significantly difference in lBU/Kg,2BU/Kg,4 BU/Kg and control groups (P>0.05) ,and it may be result of effective dose of batroxobin insufficiently.Ultrastructure in hippocampal neurons was normal in sham-operation group,but there had a remarkable apoptosis chang of ultrastructure in control group.It had a different chang of ultrastructure in all batroxobin groups.From the above results, we reckon here that the best dose of batroxobin to protect forebrain ischemia-reperfusion injury in gerbils is 8 BU/Kg.The dose is corresponding to the some experiment of batroxobin.Ultrastructure showed that brain protection of batroxobin is related to the time of intracerebroventricular injection. Batroxobin has brain protecting effect in 48 hours and 72 hours,but its effect is lower than that within 48 hours.We used immunohistochemistry technology to test the expression of Bcl-2,eNOS,VEGF and Akt after forebrain ischemia-reperfusion injury in gerbils using batroxobin 8 BU/Kg in different time of0h,1h,3h,6h,12h,24h,48h and 72h.The expression of Bcl-2,eNOS,VEGF and Akt had a remarkable increase in each time. It had significant dif...