基于MCAO模型的动物脑水肿进程研究

Study on the progression of brain edema in animals based on MCAO model

目的通过HE染色和核磁弥散加权成像(DWI)探究缺血性脑卒中(IS)后脑含水量时间变化规律和血管源性脑水肿的出现时间。方法实验分为模型组和对照组,采用线栓法制备大脑中动脉永久性栓塞模型,造模后又分21个亚组,观察不同时间点的脑水肿变化规律。采用干湿重法测脑含水量;通过HE染色观察脑组织形态学变化;使用DWI获得相对扩散系数(rADC)并计算各时间点rADC均值,观察rADC随时间的变化规律,找出数值变化的时间拐点。结果造模后9~11 h脑含水量开始增加(9 h,P=0.0810;11 h,P=0.0755);12~36 h脑含水量急速上升(12 h,P=0.0484;24 h,P=0.0002;36 h,P=0.0001);36~60 h脑含水量急速下降(48 h,P=0.0008;60 h,P=0.0304)。HE结果显示造模后即刻开始出现灰质细胞水肿和变性,白质神经纤维束从3 h开始出现空泡和海绵样变性。DWI结果示rADC值在造模后186 min时首次升高,随后又下降,因此该时间点为rADC数值变化的拐点。结论IS后3 h出现血管源性脑水肿,36 h时脑含水量达到峰值。在本研究发现的基础上,未来应基于DWI进一步明确IS患者的脑水肿变化规律,从而为IS后脑水肿的精细化治疗提供依据。

Objective To explore the temporal changes of cerebral water content and the occurrence time of vasogenic cerebral edema after ischemic stroke(IS)by HE staining and diffusion-weighted imaging(DWI).Methods The experiment was divided into model group and control group.Middle cerebral artery occlusion model was prepared by thread-embolism method.After modeling,21 subgroups were divided to observe the changes of cerebral edema at different time points.Cerebral water content was measured by dry/wet weight method.The morphological changes of brain tissue were observed by HE staining.DWI was used to obtain the relative apparent diffusion coefficient(rADC)and calculate the average rADC at each time point,observe the change rule of rADC with time,and find the time inflection point of the value change.Results The cerebral water content increased at 911 h after modeling(9 h,P=0.0810;11 h,P=0.0755),increased rapidly at 1236 h(12 h,P=0.0484;24 h,P=0.0002;36 h,P=0.0001)and decreased speedily at 3660 h(48 h,P=0.0008;60 h,P=0.0304).HE results showed that edema and degeneration of gray matter cells began to appear immediately after modeling,and vacuolation and spongiform degeneration of white matter nerve fiber bundles began to appear at 3 h.The DWI results showed that rADC value increased for the first time at 186 min after modeling,and then decreased,so this time point was the inflection point of rADC value change.Conclusion Vasogenic cerebral edema appeared at 3 h after IS,and the cerebral water content reached its peak at 36 h.On the basis of the findings of this study,the change rule of brain edema in IS patients should be further clarified based on DWI in the future,so as to provide a basis for the refined treatment of brain edema after IS.