氟达拉滨对大鼠脑缺血再灌注后STAT1影响及MRI变化  

The Influence of Fludarabine on the Expression and Activation of STAT1 and the Changes of MRI Imaging After Focal Cerebral Ischemia Reperfusion in Rats

作　　者：许倩[1] 姜春娟[1] 徐凯[1] 荣玉涛[1] 杨春[1] 刘颖[1] 

机构地区：[1]徐州医学院附属医院影像科,221002

出　　处：《临床放射学杂志》2013年第5期742-746,共5页Journal of Clinical Radiology

摘　　要：目的探讨氟达拉滨对大鼠脑缺血再灌注后信号转导子与转录激活子-1(STAT1)的影响及MRI改变。方法雄性SD大鼠40只,随机分为A组(假手术组)、B组(缺血模型组)、C组(生理盐水治疗组)、D组(氟达拉滨治疗组)。线栓法建立左侧大脑中动脉闭塞模型。每组动物均于缺血2 h再灌注24 h后行扩散加权成像(DWI)、灌注成像(PWI)、T2WI扫描,采用免疫印迹法检测缺血区STAT1、P-STAT1蛋白表达水平。结果 B、C、D组DWI示部分左侧大脑半球高信号,PWI呈现灌注缺损,ADC值降低,CBV降低,MTT延长。D组DWI异常信号区相对面积(P=0.014,0.030)、PWI灌注缺损区相对面积(P=0.018,0.022)、rMTT值(P=0.002,0.003)较B、C组小(P<0.05),rADC值(P=0.003,0.023)及rCBV值(P=0.008,0.021)较B、C组大(P<0.05)。B、C、D组DWI异常信号与PWI灌注缺损区相对面积差异无统计学意义(P=0.094,0.268,0.292>0.05)。B、C组缺血区P-STAT1较A组增加,D组P-STAT1较B、C组减少(P=0.006,0.012<0.05);各组STAT1蛋白表达水平无明显变化(P=0.588>0.05)。氟达拉滨干预后P-STAT1表达变化与rADC值变化呈负性相关(r=-0.708,P<0.05),与DWI异常信号相对面积变化呈正性相关(r=0.676,P<0.05)。结论脑缺血再灌注损伤早期给予氟达拉滨能够抑制STAT1活化、缩小脑梗死面积;MRI成像指标变化与STAT1活化阻断存在一定联系。Objective To investigate the variation of expression and activation of STAT1 and the changes of MRI after focal cerebral ischemia reperfusion in rats which were pre applicated with STAT1 inhibitor fludarabine.Methods 40 adult male Sprague-Dawley rats were randomly divided into 4 groups： Group A（sham-operated group）,Group B（ischemia-reperfusion group）,Group C（saline treatment group）,Group D（fludarabine treatment group）.The MCAO model was set up according to the method described by Zea Logna.MRI,including DWI、PWI and T2WI was performed at 2 h ischemia and 24 h reperfusion in rats.After measuring the relative areas of abnormal signal and changes of several parameters,samples taken from the abnormal signal area of MRI in rats were analyzed by Western blots using STAT1,P-STAT1,STAT3 and P-STAT3 antibodies.Results MRI Performance： hyperintensity in DWI and perfusion defection in PWI were found in the ipsilateral MCA territories in group B、C and D.CBV were significantly decreased,while MTT were significantly prolonged.In group D,the relative area of abnormal signal in DWI（P=0.014,0.030）,perfusion defection in PWI（P=0.018,0.022） and the relative value of MTT（P=0.002,0.003） were smaller than group B or C（P0.05）.The relative value of ADC（P=0.003,0.023） and CBV（P=0.008,0.021） in the ischemic region of group D were obvious greater than that of group B or C（P0.05）.The mismatch areas between PWI and DWI did not reach statistical significance（P=0.094,0.268,0.2920.05）.Western blot： there were no difference in STAT1 protein expression（P=0.5880.05）.The levels of P-STAT1 in group B or C were higher than that of group A.Compared with group B or C,group D significantly decreased the expression of P-STAT1 protein（P=0.006,0.0120.05）.The changes of P-STAT1 had a relation with the value of rADC（r=-0.708,P0.05）,and the relative area of DWI（r=0.676,P0.05）.Conclusion Fludarabine,which is administrated in the early stage of celebral ischemia-reperfusion injury,could in

关 键 词：脑缺血 磁共振成像 STAT1 氟达拉滨 

分 类 号：R743.3[医药卫生—神经病学与精神病学]