Effect Of Butylphthalide On Changes Of P38 And ERK In AD Model Rats

Objectives To determine the learning and memory ability and the morphous,observe the changes of p38 mitogen-activated protein kinase (P38MAPK) and extra-cellular singal regulate kinases(ERKs) in the brain tissue of alzheimer disease model rats,explore the role of mitogen -activated protein kinase(MAPK) in the alzheimer disease,and discuss the effect of Butylphthalide on AD.Methods Sixty healthy male Sprague-Dawley(SD) rats were selected and then devided into three groups randomly,these were the control group,the AD group,and the Butylphthalide group.The AD model was set up by injection withβ-amyloid 1-42(Aβ1-42) into the left hippocampus stereotacticly.Learning and memory functions were tested by Y-type electric maze before and sixty days after operation.The number of abnormal neurons was determined by HE staining.The deposition of amyloid and the expression levels of P38 in the region of CA1 and ERK on cortex were measured by immunohistochemistry(IH).Results1.The behavior changes of rats before and after the surgeryComparison among groups showed no significance(F=0.041, P=0.96) before operation.After operation,significance was showed among groups(F=11.682,P<0.001).Comparison between the AD group and the control group showed significance(P<0.001).Comparison between the Butylphthalide group and the AD group showed significance (P<0.001).2.HE stainingMorphology There were more normal neurons in the region of CA1 in the control group than in the AD model group.The neurons showed regular arrangement,with distinct edges and clear and obvious nucleus and nucleolus.No significant necroses of pyramidal neurons were found.In the AD group,normal neurons in the region of CA1 decreased greatly,the neurons had an irregular arrangement,and the edge of many cells was unclear.The nucleus and nucleolus of many neurons became ambiguous.The Butylphthalide group showed some neurons necrosed,the neurons had a regular arrangement.Density of the neurons in CA1 region.There was significant difference among the three groups(F=376.978,P<0.001).Compared with the control group,the AD group showed significant difference(P<0.001), Compared with the AD group,The Butylphthalide group showed significance(P<0.001).3.Expression of 6E10Brown particulate matter can be seen along the injection region by the micro- syringe in the brain tissue section of AD group and the Butylphthalide group and there was no obvious brown granular material deposition in the control group.4.Expression of P38There was significant difference among groups(F=334.594,P< 0.001).Compared with the control group,the AD group showed significant difference about the activity of P38(P<0.001).Compared with the AD group,the Butylphthalide group showed significance(P<0.001).5 Expression of ERKThere was significant difference among groups(F=228.298,P< 0.001).Compared with the control group,the AD group showed significant difference(P<0.001).Compared with the AD group,the Butylphthalide group showed significance(P<0.001).Conclusions1,The expression of P38 increased and the expression of ERK decreased in AD rats,which play the role of promote the development of AD.2,Butylphthalide may improve the learning and memory ability of AD rats by inhibiting the activity of P38 and activating the approach of ERK.