目的:探讨应用 AQP4基因沉默治疗早期脑梗死后的磁共振表现及病理改变。方法选成年 Wistar 大鼠,随机分为对照组、梗死组、治疗组,每组再分0.5、1、2、4 h 及6 h 组,每组各6只,共90只。进行右侧大脑中动脉栓塞(MCAO-梗死组)、注射无意义短发夹(short hairpin )RNA-AQP4脂质体(shRNA-AQP4+MCAO-对照组)及干扰剂(siRNA-AQP4+MCAO-治疗组)。分别进行头部 T2 WI、DWI 扫描,测量 T2 WI、DWI 高信号最大层面相对面积(rs-T2 WI、rs-DWI)及相对表观扩散系数(rADC)值,随后取对应脑组织进行病理观察,所得数据采用 SPSS 13.0软件统计分析。结果对照组与梗死组在0.5 h 的 DWI 上出现高信号,2 h 在T2 WI 上出现高信号,rs-DWI 和 rs-T2 WI 随时间而增大。除6 h 外 rs-DWI 比同时间点的 rs-T2 WI 大(P 〈0.01)。2 h 内 rADC 迅速下降,病理表现为细胞水肿;而在4 h、6 h 的 rADC 值缓慢回升,出现血管源性水肿参与的混合性水肿。治疗组 rs-DWI 缩小,与对照组比较(除6 h 外)差异有统计学意义(P 〈0.01),而各时间点的 rs-T2 WI 无明显缩小。治疗组在0.5~6 h 时 rADC 呈上升趋势,二者在0.5~4 h 时间段与对照组比较差异有统计学意义(P 〈0.01),此阶段细胞内水肿明显减轻;6 h 时间点的 rADC 与对照组比较差异无统计学意义(P 〉0.05),6 h 组仍见明显的血管源性水肿。结论早期脑梗死时 DWI 与 T2 WI 高信号面积的不匹配区为细胞水肿,是导致 ADC 值下降的病理基础。AQP4基因沉默能有效缓解细胞内水肿。DWI 及 ADC 值能及时、准确显示细胞水肿的治疗效果。T2 WI 高信号代表血管源性水肿,AQP4基因沉默无明显变化。
Objective This study investigated magnetic resonance imaging (MRI)manifestations and pathological changes after aquaporin-4 (AQP4)gene silencing in treatment of early cerebral infarction.Methods Ninety adult Wistar rats were randomly divided into con-trol group,infarction group and treatment group.All the above groups were assigned to five sub-groups according to the time point:0.5,1,2,4 and 6 hours,respectively (n= 6 for each group).For the right middle cerebral artery occlusion (MCAO-infarction group),the rats were separately injected with short hairpin RNA-AQP4 liposome (shRNA-AQP4+MCAO-control group)and in-terference agents (siRNA-AQP4 + MCAO-interference group).The rats in all groups were examined with T2 weighted image (T2 WI)and diffusion-weighted imaging (DWI).The rs-T2 WI,rs-DWI and relative apparent diffusion coefficient (ADC)of the big-gest high-signal-intensity layer on T2 WI and DWI were measured.Corresponding brain tissue was collected for pathological observation.The data were analyzed using SPSS 13.0 software.Results Identical changes were detected between control and infarction groups.The high-signal intensity was found on DWI at 0.5 hour and on T2 WI at 2 hours after MCAO.rs-DWI and rs-T2 WI increased with time.The value of relative ADC decreased quickly within 2 hours after MCAO,and cytotoxic edema was significantly aggravated.The value of relative ADC increased slowly at 4 and 6 hours,but angioedema was detected during this period.There was significant change in relative ADC between the treatment and control groups at 0.5 to 4 hours (P 〈 0.01)and cytotoxic edema was significantly lightened.But there was no significant difference in relative ADC between treatment and control groups at 6 hours (P 〉0.05).However,angioedema was visible in this group at 6 hours.Above results confirmed that during early cerebral infarction,the differential regions of DWI and T2 WI high-signal area were considered as cytotoxic edema,which was the pathologic&