The Protecting Effect Of FGF1 And FGFR1 In The Process Of Ischemia Preconditioning Of The SD Rat

OBJECTIVE:To investigate the changes of expression of both FGF-1 and FGFR-1 in the process of ischemia tolerance induced by global cere- bral ischemia preconditioning(IP)in the adult SD rat and to explore their role in ischemic tolerance.MATERIALS AND METHODS:Modified four-vessel occlusion rat models was used in this study.120 healthy adult Sprague-Dawley(SD) rats were divided randomly into 4 groups,and each group was divided into 5 subgroups according to different time points that were designed in advance.Group A:sham-operated control group,The subgroup A1,A3, A7,A14 and A21 were raised respectively 1 day,3 days,7 days,14 days and 21 days after sham operation;Group B:Control group to be given ischemia preconditioning for 3 minuts,subgroup B1,B3,B7,B14 and B21 were respectively reperfused for 1 day,3 days,7 days,14 days and 21 days;Group C:Control group to be given ischemia preconditioning for 9 minuts,subgroup C1,C3,C7,C14 and C21 were respectively reperfused for 1 day,3 days,7 days,14 days and 21 days;Group D:Trial group,subgroup D1,D3,D7,D14 and D21 were reperfused respectively for 1 day,3 days,7 days,14 days and 21 days followed 3 minuts' ischemia,then all be given ischemia for 9 minuts.Rats of Group A, Group B and Group C were decapitated and the brains were taken out when raise or reperfusion finished,and so did the rats of group D 7 days after 9 minuts' ischemia.The histopathological changes and ultrastructure of cerebral hippocampus CA1 subarea were exmined by HE staining and the expressions of FGF-1 and FGFR-1 were studied by immunohistochemistry. All the experimental data were analyzed to be deployed one-way analysis of variance by SPSS 13.0 software.RESULTS:HE-stained slices were observed by microscope,all results showed:There were no significant changes of cellular necrosis in subgroups of A1,A3,A7,A14,A21,B1,B3,B7,B14 andB21;Mass cellular necrosis were observed in subgroups of C1,C3,C7,C14,C21, D1,D14 and D21,part of neurons of D3 and D7 were necrotic,and neuronal survival of D3 was highest among all subgroups of group D. immunohistochemical staining of FGF-1 showed:Positive stains were rare inhippocampusinsubgroupsofA1,A3,A7,A 14,A21,B1, B3,B7,C1,C3 and C7;Positive stains were abundant in hippocampus in subgroups of B14,B21,C14,C21,D3,D7,D14 and D21. immunohistochemical staining of FGF-1 showed:Positive stains were rare inhippocampus in subgroups of A1,A3,A7,A14,A21,B14, B21,C14,C21;Positive stains were abundant in hippocampus in subgroups of B1,B3,B7,C1,C3,C7,D1,D3,D7,D14,D21.Compared with each other of groups,due to IP,the quantum of survive neuron and expression ofFGF-1 and FGFR-1 were different significantly. CONCLUSIONS:(1)after single cerebral ischemia for 3 minutes, brain can got the protective effect against the following deadly cerebral ischemia;especially in the third day;(2)single cerebral ischemia for both 3 minutes and 9 minutes,the expression of FGF-1 and FGFR-1 had a strengthen tendency,after single cerebral ischemia for 3 minutes and respective reperfusion for 1 day,3 days,7 days,14 days and 21 days, then all for cerebral ischemia once more for 9 minuts,the expression of FGF-1 and FGFR-1 have a further expression;(3)FGF-1 and FGFR-1 played a role in the mechanism of ischemic tolerant effect,and the level of FGF-1 and FGFR-1 's expression was related to the protective effect on brain.