腦水腫的發(fā)病機理及藥物治療課件

1、腦水腫的發(fā)病機理及藥物治療,醫(yī)院及講者信息,1,腦水腫的發(fā)病機理及藥物治療,腦水腫,腦實質(zhì)聚集過量液體,2,腦水腫的發(fā)病機理及藥物治療,腦水腫分類,血管源性腦水腫 血腦屏障受損所致，大量液體和血管內(nèi)蛋白質(zhì)積聚于腦白質(zhì)細胞間隙 常見于腦創(chuàng)傷、腦出血、腦缺血的第二階段,3,腦水腫的發(fā)病機理及藥物治療,腦水腫分類,細胞毒性腦水腫 ATP失功、細胞內(nèi)外Na+轉(zhuǎn)運失衡所致 水腫液分布于腦細胞內(nèi)，細胞間隙不但不擴大，反而縮小 常見于腦缺血和肝衰,4,腦水腫的發(fā)病機理及藥物治療,腦水腫動物實驗模型,凍傷模型 液壓沖擊傷模型 腦出血模型 水中毒模型 肝損模型,5,腦水腫的發(fā)病機理及藥物治療,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,凍傷模型 主要用于血管源性腦水腫的試驗模型 凍傷直接破壞血管細胞，導致不可逆的血腦屏障損傷 特點：試驗的可重復性及受傷面積的準確性,6,腦水腫的發(fā)病機理及藥物治療,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,液壓沖擊傷模型 模擬腦創(chuàng)傷引發(fā)的腦水腫 可誘導各種降解酶如MMP-9的激活，導致血管基底膜的降解 可觀察到炎性介質(zhì)的增加及巨

4、噬細胞的浸潤,7,腦水腫的發(fā)病機理及藥物治療,The Cerebral Hemorrhage Model,通過腦實質(zhì)內(nèi)注射膠原蛋白酶破壞血管基底膜或者注射自體血制備腦出血模型（ICH model） 常見的蛛網(wǎng)膜下腔出血模型（SAH model）包括：單側(cè)出血、雙側(cè)出血、血管內(nèi)穿刺模型 可同時觀察到血管源性腦水腫及細胞毒性腦水腫,8,腦水腫的發(fā)病機理及藥物治療,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,腦水腫的發(fā)病機理及藥物治療,The Liver Failure Model,急性或慢性肝細胞失功引發(fā)的肝衰會誘導肝性腦病，造成中樞神經(jīng)組織嚴重失功。 急、慢性肝衰導致的腦水腫發(fā)病機制不同 急性肝衰，ICP上升；慢性肝衰很少觀察

6、到ICP上升 肝衰模型產(chǎn)生的腦水腫為細胞毒性腦水腫 星形細胞腫脹 血腦屏障未見損害 一般采用硫代乙酰胺誘導肝細胞損傷 氨基半乳糖誘導急性肝衰 膽管結(jié)扎或門腔靜脈吻合術(shù)誘導慢性肝衰,10,腦水腫的發(fā)病機理及藥物治療,評估腦水腫方法,干濕稱重法 重量法 MRI檢測法,11,腦水腫的發(fā)病機理及藥物治療,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,腦水腫的發(fā)病機理及藥物治療,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,腦水腫的發(fā)病機理及藥物治療,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,腦水腫的發(fā)病機理及藥物治療,腦水腫關(guān)鍵因子及治療,VEGF、MMPs、AQPs、NKCC1、ETB-R、GR,15,腦水腫的發(fā)病機理及藥物治療,腦水腫生成關(guān)鍵因子,16,腦水腫的發(fā)病機理及藥物治療,抗水腫治療藥物,17,腦水腫的發(fā)病機理及藥物治療,麥通納作用機制,作用與GCR/NFB 信號通路，抗炎作用 上調(diào)GC受體表達，抑制 NFB的活化1,2 抑制TNF-,IL-1等炎癥因子的產(chǎn)生3 封閉毛細血管，減少毛細血管壁上小孔的數(shù)量和直徑4 維持正常血管通透性 抑制局部炎癥細胞滲出 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,腦水腫的發(fā)病機理及藥物治療,麥通納顯著提高糖皮質(zhì)激素受體的表達,脂多糖(LPS)誘導的炎癥小鼠模型中，GR蛋白水平表達顯著下降（p0.05) ； 麥通納顯著提高GR蛋白的表達，不僅在麥通納組，且在脂多糖+麥通納組, GR蛋白水平顯著高于對照組（p0.01) a,對照組；b,麥通納鈉組（3.6mg/kg);c,LPS組；d,地塞米松（4.0mg/kg） +LPS組；f,麥通納（1.8mg/kg)+LPS組;g,麥通納（3.6mg/kg) )+LPS組,N. Jiang et al. / Phytomedicine 18 (2011) 1276 1284,19,腦水腫的發(fā)病機理及藥物治療,麥通納協(xié)同激素抗炎消腫,低劑量可的松、麥通納聯(lián)合給藥6h，水腫顯著減輕,N. Jiang et al. / Phytomedici