创伤性脑水肿基因干扰AQP4治疗后改变及扩散加权成像特征  

The change of traumatic cerebral edema and DWI manifestation in rat treated with AQP4 gene silencing

作　　者：张程程[1] 鲁宏[1] 

机构地区：[1]中南大学湘雅医学院附属海口医院海口市人民医院放射科,海南海口570208

出　　处：《实用放射学杂志》2015年第12期2060-2065,共6页Journal of Practical Radiology

基　　金：国家自然科学基金项目（81160181）;海口市重点科技计划项目（2015030）.

摘　　要：目的 探讨基因沉默水通道蛋白-4（AQP4）治疗脑创伤后病理、AQP4表达及其扩散加权成像（DWI）特征。方法 健康成年雄性SD大鼠180只，制作脑创伤模型，按随机数字表法分为创伤组（A组）、安慰剂治疗组（B组）、干扰剂治疗组（C组），按创伤后时间点分为1 h、6 h、24 h、48 h、72 h、7 d 6个亚组，每组10只，各组分别于上述时间点行DWI（n=4），随后观察损伤区的病理改变（n=2）、Western-blot检测AQP4蛋白表达（n=8），最后统计分析rs-T2WI、rs-DWI、rADC、病理变化以及AQP4蛋白表达的关系。结果 B组与A组的变化一致，AQP4蛋白在1 h表达下调，6 h最低，之后升高至24 h达峰值，48 h缓慢下调,72 h出现第2个峰值，随后下降至7 d。rs-T2WI及rs-DWI随着损伤时间延长而逐渐增大，以24 h、72 h及7 d组增加明显。ADC值在1 h时升高， 6 h最高，随后下降，24 h时降至最低，之后上升至48 h，72 h出现第2次下降，随后上升至7 d。2组对比AQP4蛋白表达及rs-T2WI、rs-DWI、rADC值差异无统计学意义（P＞0.05）。C组与A组对比AQP4蛋白表达在24 h和72 h明显下调；rs-T2WI及rs-DWI在24 h、72 h和7 d明显缩小；rADC值在24 h和72 h明显回升。A组及B组1 h主要病理改变为血管源性水肿，6 h开始出现细胞内水肿,24 h细胞水肿明显加重出现第1水肿高峰,48 h水肿稍减轻，72 h细胞水肿继续加重并出现第2个水肿高峰，7 d细胞水肿减轻，但血管源性水肿有加重趋势并可见组织坏死、大量炎性细胞浸润、胶质增生。C组于24 h、72 h的细胞水肿明显减轻，7 d的血管源水肿及组织坏死、炎性细胞明显缓解。结论 AQP4-siRNA治疗可减轻细胞水肿和缓解脑创伤晚期的血管源性水肿及炎性反应，但对早期脑创伤的血管源性水肿的治疗无明显效果。功能磁共振DWI可以间接反映脑创伤组织水肿的演变过程，并可在一定程度上监测治疗效果�Objective To investigate the changes in the expression of AQP4 and the diffusion-weighted imaging（DWI ） in traumatic injury rat brain tissue before and after therapy with AQP4 gene silencing. Methods 180 healthy adult Wistar rats were used to establish models of TBI. Rats were randomly assigned to the TBI groups （A） , placebos groups （B） and interference groups （C） （ n = 10 ）, six time points were investigated after injury（1 h,6 h,24 h,48 h,72 h and 7 d）. All the brains were tested with a final DWI at each time points to measure rs-T2WI,rs-DWI and rADC of brain tissue of the injured side after which they were euthanized（ n= 4）, then the pathological changes of the injured side were examined（n= 2）, the AQP4 protein expression was tested with Western blot（n= 8）. The data of the relationship between rs-T2 WI,rs-DWI, rADC, the pathological changes of the injured side and the AQP4 protein expression after brain injury was analyzed with SPSS 18.0 statistical software. Results The TBI groups of AQP4 protein decreased at 1 h, and then came to the bottom at 6 h,and then increased to the peak at 24 h,following a slow down-regulation at 48 h,while the second peak at 72 h,at last stayed down till 7 d. While rs-T2WI and rs-DWI increased gradually with time going,it rised obviously especially the groups of 24 h,72 h and 7 d. ADC value raised at 1 h,and then came to the summit at 6 h;and then decreased,following a low ebb at 24 h,while raised at 48 h,then the second decrease appeared at 72 h, and remain high value until 7 d. Compared with TBI groups, AQP4 protein expression, rs-T2WI, rs-DWI, rADC showed no significant difference （P〉0.05） in placebo groups. The expression of AQP4 protein was significantly down regulated at 24 h and 72 h between interference groups and contusion group,while rs-T2WI and rs-DWI decreased obviously at 24 h,72 h and 7 d;rADC increased obviously at 24 h and 72 h. The main pathological changes of TBI groups and placebo groups at 1 h were vasogenic edema,and the

关 键 词：脑创伤 脑水肿 磁共振成像 扩散加权成像 水通道蛋白 基因沉默 

分 类 号：R651.15[医药卫生—外科学] R742.7[医药卫生—临床医学]