脑水肿的发病机理及药物治疗课件

1、脑水肿的发病机理及药物治疗,医院及讲者信息,1,脑水肿的发病机理及药物治疗,脑水肿,脑实质聚集过量液体,2,脑水肿的发病机理及药物治疗,脑水肿分类,血管源性脑水肿 血脑屏障受损所致，大量液体和血管内蛋白质积聚于脑白质细胞间隙 常见于脑创伤、脑出血、脑缺血的第二阶段,3,脑水肿的发病机理及药物治疗,脑水肿分类,细胞毒性脑水肿 ATP失功、细胞内外Na+转运失衡所致 水肿液分布于脑细胞内，细胞间隙不但不扩大，反而缩小 常见于脑缺血和肝衰,4,脑水肿的发病机理及药物治疗,脑水肿动物实验模型,冻伤模型 液压冲击伤模型 脑出血模型 水中毒模型 肝损模型,5,脑水肿的发病机理及药物治疗,The Cold

2、Injury Model,Cold injury is performed by inflicting freeze stimulation on the hemisphere of the skull of the animal,After cold injury, BBB disruption is indicated by evaluating extravasation of Evans blue dye,冻伤模型 主要用于血管源性脑水肿的试验模型 冻伤直接破坏血管细胞，导致不可逆的血脑屏障损伤 特点：试验的可重复性及受伤面积的准确性,6,脑水肿的发病机理及药物治疗,The Fluid

3、 Percussion Injury (FPI) Model,Fluid percussion injury is performed by an injury to the intact dura after craniectomy by impacts of rapidly pushed fluid (B1,B2). As well as cold injury, the extravasation of Evans blue dye is observed (B3,液压冲击伤模型 模拟脑创伤引发的脑水肿 可诱导各种降解酶如MMP-9的激活，导致血管基底膜的降解 可观察到炎性介质的增加及巨

4、噬细胞的浸润,7,脑水肿的发病机理及药物治疗,The Cerebral Hemorrhage Model,通过脑实质内注射胶原蛋白酶破坏血管基底膜或者注射自体血制备脑出血模型（ICH model） 常见的蛛网膜下腔出血模型（SAH model）包括：单侧出血、双侧出血、血管内穿刺模型 可同时观察到血管源性脑水肿及细胞毒性脑水肿,8,脑水肿的发病机理及药物治疗,The Water Intoxication Model,induces a relative decrease of extracellular Na+ concentration， best reflects simulation o

5、f hyponatremia produced by intraperitoneal loading of excessive distilled water corresponding to 10%40% of the body weight of experimental animals adopted as a model of cytotoxic edema,9,脑水肿的发病机理及药物治疗,The Liver Failure Model,急性或慢性肝细胞失功引发的肝衰会诱导肝性脑病，造成中枢神经组织严重失功。 急、慢性肝衰导致的脑水肿发病机制不同 急性肝衰，ICP上升；慢性肝衰很少观察

6、到ICP上升 肝衰模型产生的脑水肿为细胞毒性脑水肿 星形细胞肿胀 血脑屏障未见损害 一般采用硫代乙酰胺诱导肝细胞损伤 氨基半乳糖诱导急性肝衰 胆管结扎或门腔静脉吻合术诱导慢性肝衰,10,脑水肿的发病机理及药物治疗,评估脑水肿方法,干湿称重法 重量法 MRI检测法,11,脑水肿的发病机理及药物治疗,Wet-Dry Weight Method,a common and simple method invasive and not performed in patients based on the weight measurement of brain tissue before and afte

7、r complete dehydration Water content (%) = 100 (wet weight dry weight) /wet weight Water content = (wet weight dry weight)/dry weight Tissue swelling (%) = 100 (final wet weight initial wet weight) /initial wet weight wet weight：The weight before dehydration dry weight：the weight after dehydration,1

8、2,脑水肿的发病机理及药物治疗,The Gravimetric Method,The gravimetric technique is based on calculating the percentage of water from measuring the density of the tissue in experimental animals This method is also invasive and not performed in patients Advantages: higher sensitivity use of smaller pieces of tissue,

9、13,脑水肿的发病机理及药物治疗,Magnetic Resonance Imaging (MRI,a noninvasive method，used for evaluating brain edema in patients and experimental animals Two Index: apparent diffusion coefficient（ADC） reduced ADC values correlate with cytotoxic edema T2 imaging the increased T2 values reflect the development of va

10、sogenic edema,14,脑水肿的发病机理及药物治疗,脑水肿关键因子及治疗,VEGF、MMPs、AQPs、NKCC1、ETB-R、GR,15,脑水肿的发病机理及药物治疗,脑水肿生成关键因子,16,脑水肿的发病机理及药物治疗,抗水肿治疗药物,17,脑水肿的发病机理及药物治疗,麦通纳作用机制,作用与GCR/NFB 信号通路，抗炎作用 上调GC受体表达，抑制 NFB的活化1,2 抑制TNF-,IL-1等炎症因子的产生3 封闭毛细血管，减少毛细血管壁上小孔的数量和直径4 维持正常血管通透性 抑制局部炎症细胞渗出 提高SOD活性，清除氧自由基5,1，EXPERIMENTAL AND THERAP

11、EUTIC MEDICINE 6: 419-422, 2013 2，Mol Pharmacol. 2010 May;77(5):818-27 3，J Zhejiang Univ Sci B. 2005 Jan;6(1):28-32 4，Arzneimittelforschung. 1970 May;20(5):699-703 5，Yao Xue Xue Bao. 2004 Jun;39(6):419-23,18,脑水肿的发病机理及药物治疗,麦通纳显著提高糖皮质激素受体的表达,脂多糖(LPS)诱导的炎症小鼠模型中，GR蛋白水平表达显著下降（p0.05) ； 麦通纳显著提高GR蛋白的表达，不仅在麦通纳组，且在脂多糖+麦通纳组, GR蛋白水平显著高于对照组（p0.01) a,对照组；b,麦通纳钠组（3.6mg/kg);c,LPS组；d,地塞米松（4.0mg/kg） +LPS组；f,麦通纳（1.8mg/kg)+LPS组;g,麦通纳（3.6mg/kg) )+LPS组,N. Jiang et al. / Phytomedicine 18 (2011) 1276 1284,19,脑水肿的发病机理及药物治疗,麦通纳协同激素抗炎消肿,低剂量可的松、麦通纳联合给药6h，水肿显著减轻,N. Jiang et al. / Phytomedici