摘要
【目的】应用鼠脑创伤模型观察靶向水通道蛋白4(Aquaporin 4,AQP-4)的小RNA干扰(siRNA)技术对脑水肿的治疗效果。【方法】构建沉默AQP-4 mRNA表达的siRNA质粒;液压打击法建立大鼠脑创伤(traumatic brain injury,TBI)模型,分TBI组、空载质粒组和AQP-4 siRNA治疗组;提取第1、3、5、7天脑组织总RNA,RT-PCR方法检测AQP-4的mRNA表达;干/湿比重法和Evans蓝测定法观察大鼠TBI后不同时相脑组织含水量和血脑屏障通透性改变;实验动物予以神经功能缺陷综合评分。【结果】RT-PCR结果显示siRNA质粒可有效沉默AQP-4在受损脑组织的表达;与TBI组和空载质粒组比较,AQP-4 siRNA治疗组在减少受损脑组织含水量、降低血脑屏障通透性,以及改善动物神经功能方面均有明显好转,各检测时间点与TBI组和空载质粒组比较均存在统计学差异(P<0.05)。【结论】靶向AQP-4的siRNA技术通过对AQP-4的有效沉默可明显减轻TBI后的脑水肿程度,发挥良好的治疗效果。
[Objective] Objective To observe the treatment effect of siRNA targeting aquaporin 4 on cerebral edema following traumatic brain injury. [Methods] To construct siRNA targeting aquaporin 4, and establish the TBI models in rats. The animals were divided into 3. [Results] TBI group, unladen plasmid group, and AQP- 4 siRNA group. Then extracted total mRNA on theist, 3rd, 5th, and 7th day for RT - PCR test. The changes of brain water content and per- meability of blood- brain barrier were measured by the methods of wet and dry weight and Evans blue fluorometry. All the rats were given a mark for their nerve function on the 7th day. [Conlusions] RT - PCR results showed that siRNA can effectively silence the AQP - 4 expression in damaged brain tissue. Compared with TBI group and unladen plasmid group, AQP - 4 siRNA group showed a better effect on lessening brain edema level and reducing permeability of the blood - brain barrier, as well as it enhancing rats nerve function. Conclusion The application of siRNA targeting aquaporin 4 may effectively lessen brain edema following traumatic brain injury, and show a good treatment effect.
出处
《武警医学院学报》
CAS
2009年第6期473-476,共4页
Acta Academiae Medicinae CPAPF
基金
天津市科委攻关课题基金(06YFSZSF01200)
关键词
水通道蛋白
RNA干扰
颅脑创伤
Aquaporin
RNA Interference
Traumatic Brain Injury
作者简介
【作者简介】柴慈婧（1979-），女，籍贯天津市，本科，医师，主要从事老年病学的研究。
【通讯作者】刘晓智，Tel：022—60578827；E—mail：lxz0907@yahoo．com．cn。
