摘要
目的探讨水通道蛋白4(AQP4)在缺血半暗带(IP)中的表达规律。方法将健康Wistar大鼠36只,体重300～400g,雌雄不拘,数字表法随机分为对照组(6只)和栓塞组(30只);栓塞组又分为大脑中动脉栓塞(MCAO)后15min、30min、1h、3h、6h及24h组,每组各5只大鼠;对照组的大脑中动脉不栓塞,其余操作同栓塞组。对各组行脑部T1WI、T2WI和扩散加权成像(DWI)扫描。界定影像半暗带,计算影像半暗带和中心梗死区的相对表观扩散系数(rADC1和rADC2),将缺血脑组织进行红四氮唑(TTC)染色,并与扩散加权成像(DWI)对比。取最大层面的缺血半暗带组织进行病理观察、免疫组织化学及逆转录聚合酶链反应(RTPCR)实验,用图像分析检测AQP4的表达变化。结果对照组的MRI未见异常,相对表观扩散系数及AQP4表达无明显改变。栓塞组于15min即在DWI上出现高信号;栓塞后1h在T2WI出现高信号,rADC1在24h内呈下降趋势,在1h内下降最明显,从15min的(70.4±6.9)%下降到1h的(53.5±10.9)%;而rADC2呈现先降后升的变化规律,从15min的(71.4±6.6)%下降到3h的(45.7±10.5)%,然后回升到24h的(78.7±11.5)%。在24h内,AQP4基因表达逐渐上升,从15min的0.42±0.05上升到24h的1.18±0.12,与rADC1呈显著负相关(r=-0.966,P<0.001)。病理学观察,缺血半暗带组织呈细胞内水肿改变。结论细胞内水肿是脑缺血半暗带组织的病理基础之一,AQP4表达增强是缺血半暗带形成的重要原因,半暗带组织的rADC值下降可以间接反映AQP4表达上升的水平。
Objective The aim of this study was to investigate the aquaporin-4(AQP4) expression in the ischemic penumbra tissues.Methods Thirty-six Wistar rats were divided into 7 groups randomly, including control group(n=6) and occluded groups(n=30). The occluded groups were studied after the right middle cerebral artery of the rats unilaterally occluded(MCAO) at an interval of 15 min, 30 min, 1 h, 3 h, 6 h and 24 h, respectively(n=5 for each group). The operation process of the control group was the same as the occluded group except occluded MCAO. Then all rats were imaged with T_1WI, T_2WI and diffusion weighted-imaging(DWI). The brain tissue, according to the method by LIU Meili reported, was regarded as the area of the graphic penumbra. The relative apparent diffusion coefficient of the graphic-penumbra (rADC_1) and the center infarction(rADC_2)(ratios between the values of the occluded side and the opposite side) were calculated. The animals were sacrificed and perfused with the mixture solution consisting of TTC at different time intervals. The graphic-penumbra of the biggest layer of the ischemic cerebral tissue which corresponded to the DWI was examined with immunohistochemistry and RT-PCR. Meanwhile, histologic examination was performed at same site of the lesion. Results There were no significant changes on MRI, the relative apparent diffusion coefficient and the expression of the AQP4. The abnormal high intensity was found on DWI at 15 min after MCAO. T_2WI detected the lesion at 1 h after MCAO. The value of the rADC_1 decreased within 24 h after MCAO in ischemic penumbra, especially, it descended quickly within 1 h after MCAO, from(70.4±6.9)% at 15 min to(53.5±10.9)% at 1 h. Whereas, in the infarct tissue, the changes of the rADC_2 had a rule of decrease from(71.5±6.6)% at 15 min to(45.7±10.5)% at 3 h at first time, and then follow an increasing up to(78.7±11.5)% at 24 h after MCAO. The expression of AQP4 increased gradually within 24 h after MCAO, from 0.42±0.05 at 15 min to 1.18±0.12 at 24 h, it showed negative relationship with the rADC_1 in the ischemic penumbra (r= -0.966,P<0.001), where the major pathologic changes were intracellular edema. Conclusion The results imply that the intracellular edema is one of the important pathologic characteristics of the ischemic penumbra. The high expression of AQP4 may play a key role in the ischemic penumbra. The decreasing of rADC values in the ischemic penumbra maybe provide earlier and more precise evaluation of the level of the AQP4 expression.
出处
《中华放射学杂志》
CAS
CSCD
北大核心
2005年第6期604-607,共4页
Chinese Journal of Radiology
基金
国家自然科学基金资助项目(30471646)
