中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (7): 1082-1087.doi: 10.4103/1673-5374.160099

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

水通道蛋白4基因沉默对早期脑梗死后损伤神经元的保护

  

  • 收稿日期:2015-06-13 出版日期:2015-07-24 发布日期:2015-07-24

Aquaporin-4 gene silencing protects injured neurons after early cerebral infarction

Zhan-ping He, Hong Lu   

  1. Department of Radiology, Affiliated Haikou Hospital of Xiangya School of Medicine, Central South University (Department of Radiology, Haikou Municipal People’s Hospital), Haikou, Hainan Province, China
  • Received:2015-06-13 Online:2015-07-24 Published:2015-07-24
  • Contact: Hong Lu, Ph.D., cqluh@sohu.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 30960399; a grant from Hainan Provincial International Cooperation Project of China, No. Qiongke (2012)65; a grant from Hainan Provincial Health Department Project of China, No. 2011-SWK-10-136/Qiongwei2011-65.

摘要:

水通道蛋白4表达上调与早期脑梗死后细胞水肿密切相关,弥散加权成像检测的脑梗死面积和表观弥散系数可显示细胞水肿和水通道蛋白4的表达情况。我们建立右侧大脑中动脉栓塞模型大鼠,将siRNA-水通道蛋白4立即注射于右侧基底节区。头部T2WI、DWI扫描显示,模型大鼠T2WI、DWI检测的高信号面积、相对表观弥散系数在建模后0.5-6 h均呈上升趋势。水通道蛋白4基因沉默大鼠在建模后0.5-4.0 h其T2WI、DWI检测的高信号面积、相对表观弥散系数增高,脑细胞水肿明显减轻;建模后6 h虽然表观弥散系数与模型组相比差异不明显,但仍可见明显的血管源性水肿。结果说明,水通道蛋白4基因沉默能有效减轻脑梗死后的细胞内水肿,表观弥散系数、T2WI、DWI检测的高信号面积能及时准确显示脑梗死后脑细胞水肿的治疗效果。

关键词: 神经再生, 脑损伤, 大脑中动脉闭塞, 脑缺血, 细胞毒性水肿, 血管性水肿, 磁共振成像, 弥散加权成像, 病理学, 透射电子显微镜, 水通道蛋白, 基因沉默, 国家自然科学基金

Abstract:

Aquaporin-4 regulates water molecule channels and is important in tissue regulation and water transportation in the brain. Upregulation of aquaporin-4 expression is closely related to cellular edema after early cerebral infarction. Cellular edema and aquaporin-4 expression can be determined by measuring cerebral infarct area and apparent diffusion coefficient using diffusion-weighted imaging (DWI). We examined the effects of silencing aquaporin-4 on cerebral infarction. Rat models of cerebral infarction were established by occlusion of the right middle cerebral artery and siRNA-aquaporin-4 was immediately injected via the right basal ganglia. In control animals, the area of high signal intensity and relative apparent diffusion coefficient value on T2-weighted imaging (T2WI) and DWI gradually increased within 0.5–6 hours after cerebral infarction. After aquaporin-4 gene silencing, the area of high signal intensity on T2WI and DWI reduced, relative apparent diffusion coefficient value was increased, and cellular edema was obviously alleviated. At 6 hours after cerebral infarction, the apparent diffusion coefficient value was similar between treatment and model groups, but angioedema was still obvious in the treatment group. These results indicate that aquaporin-4 gene silencing can effectively relieve cellular edema after early cerebral infarction; and when conducted accurately and on time, the diffusion coefficient value and the area of high signal intensity on T2WI and DWI can reflect therapeutic effects of aquaporin-4 gene silencing on cellular edema.

Key words: nerve regeneration, middle cerebral artery occlusion, cerebral ischemia, cytotoxic edema, angioedema, magnetic resonance imaging, diffusion-weighted imaging, aquaporin-4, gene silencing