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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 effects of fludarabine on signal transducer and activator of transcription - 1 (STAT1) and its changes after cerebral ischemia / reperfusion in rats. Methods Forty male Sprague-Dawley rats were randomly divided into three groups: sham-operated group A, sham-operated group B, ischemia-reperfusion group C, saline-treated group D and fludarabine-treated group. Thread occlusion model was established in the left middle cerebral artery occlusion. The rats in each group were subjected to diffusion-weighted imaging (DWI), perfusion imaging (PWI) and T2WI scanning at 24 hours after ischemia for 24 hours. The expression of STAT1 and P-STAT1 protein in ischemic area were detected by Western blot. Results In group B, C, and D, the left hemisphere of the left hemisphere was marked by DWI. The perfusion defect of PWI was observed. The ADC value was decreased, the CBV was decreased and the MTT was prolonged. The relative area of DWI abnormal signal area (P = 0.014,0.030) and the relative area of PWI perfusion defect area (P = 0.018,0.022) in group D were smaller than those in group B and C (P <0.05) , rADC (P = 0.003,0.023) and rCBV (P = 0.008,0.021) than B, C group (P <0.05). There was no significant difference in the relative area between DWI and PWI perfusion in groups B, C and D (P = 0.094,0.268,0.292> 0.05). P-STAT1 in group B and C increased compared with group A, and P-STAT1 in group D decreased compared with group B and C (P = 0.006,0.012 <0.05). There was no significant change in STAT1 protein expression in each group (P = 0.588> 0.05). The change of P-STAT1 expression was negatively correlated with the change of rADC (r = -0.708, P <0.05) after fludarabine intervention, and positively correlated with the relative area of abnormal signal of DWI (r = 0.676, P <0.05). Conclusion Fludarabine can inhibit the activation of STAT1 and reduce the area of cerebral infarction in the early stage of cerebral ischemia-reperfusion injury. The changes of MRI imaging indexes may be related to the block of STAT1 activation.