Progress in Pathophysiology Mechanism of Intracranial Hemorrhage<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

安立新^*　博士研究生
王保国^#　教授
^*首都医科大学2003级博士班, 北京100054
^#中国医学科学院首都医科大学附属北京天坛医院, 麻醉科, 北京100050

Li-xin An^*, Bao-guo Wang^#
*Capital University of Medical Sciences, Beijing 100054, China
^#Department of anesthesia, Beijing Tiantan Hospital, Capital University of Medical Sciences, Chinese Academy of Medical
Sciences, Beijing 100050, China

ABSTRACT

This article summarized the pathophysiology mechanism of intracranial hemorrhage (ICH). The important pathological changes after ICH include hematoma enlarging and it's pressure effect, changes of local cerebral blood flow, poison effect of coagulum and cerebral edema. The effects of blood components including thrombin, hemoglobin, blood plasma protein, leucocyte and alexin on the surrounding tissue of hematoma and the useful values for clinical therapy were reviewed.
　　Key words: Intracranial hemorrhage; Pathophysiology; Mechanism
　　Corresponding author：Bao-guo Wang, MD; Email: wbgttyy@sina.com

　　一般来讲，血肿越大，rCBF下降越明显，丘脑出血rCBF下降较壳核出血更显著，血肿周围脑组织低灌注状态更为明显。ICH后血肿周围rCBF下降，其所累及的范围远远大于出血区，且水肿区域与rCBF下降范围基本一致，但rCBF的变化和水肿严重程度在时间上不同步，rCBF在ICH后1小时内急剧进行性下降，4小时已呈回升趋势，而脑水肿在24小时内进行性发展，脑水肿高峰期晚于rCBF下降。
　　rCBF最初的下降源于血肿占位效应引起的局部组织压迫所致的微循环障碍。rCBF的回升与血肿占位效应所致的颅内压增高及最初的CBF下降所促发的脑血流自身调节有关。损伤区周围软膜动脉和小动脉发生血管扩张，用以代偿血肿周围缺血组织的脑血流量； 而再灌注损伤则反映了一个局部炎症反应、或与淀粉样血管变性有关、或与颅内出血有关的脑血流自身调节功能的障碍。后期rCBF再一次降低可归结为脑出血后血管活性物质的释放所引起的脑血管痉挛和脑水肿的发生。同时，血管痉挛、微循环障碍以及血脑屏障破坏也可引起血管源性脑水肿的发生，这些综合因素导致颅内压增高，进而引起局部脑血流量的再次下降^[11]。血肿远隔区CBF下降主要由于血管活性物质释放所引起的脑血管痉挛。此外，远隔区rCBF下降可能还与神经机能联系不全有关，脑出血发生后脑组织移位所造成的血供障碍、颅内压增高以及脑水肿形成等也可使远隔区rCBF持续处于较低水平^[12]。<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

三、脑水肿
　　脑出血后脑水肿形成是导致脑组织结构改变和功能损伤的重要原因之一，脑水肿产生迅速，在脑出血发生后l～2小时即可出现，并进行性加重，出血后24小时达到高峰，持续4～5天开始吸收。血液凝固和血凝块回缩、凝血酶、缺血和再灌注损伤、血肿占位效应引起的周围组织机械损伤以及血脑脊液屏障通透性增加都是脑出血后脑水肿形成的原因。血肿邻近部位的水肿是由于血脑屏障破坏、细胞毒性及渗透活性物质所致，血肿远隔区水肿主要是由于组织缺血及血管源性水肿区水肿液沿纤维扩散所致。在脑出血超急性期(<4小时)，水肿为渗透性脑水肿；在急性期(4～24小时)为血管源性水肿；而后期则可发生细胞毒性水肿；如果伴有梗阻性脑积水，则可出现间质性脑水肿。
　　1. 血液凝固及血凝块回缩在超急性期脑出血周围组织脑水肿形成中的作用
　　Wagner等^[13]将猪的自体血注入脑叶制备了脑叶出血模型，并分别在注血后的l、3、5、8小时取样观察，结果显示: 在注血后l小时就可观察到血肿周围出现水肿区；在注血后3小时，用免疫组织化学方法测得水肿区内存在血浆蛋白和纤维蛋白，尽管此时血脑屏障完整， 但仍可见血肿周围有明显的水肿形成，这说明水肿区蛋白来自血肿本身。正常情况下，细胞外间隙血浆蛋白含量很低，当脑出血发生后血肿内大量蛋白渗入到血肿周围组织间隙内，导致血肿周围局部渗透压增高，从而使血液中的水份渗入到脑组织内。此外，血肿形成后由于血块回缩使血肿腔的静水压降低，这也将导致血液中的水份渗入到脑组织内形成水肿。Xi等^[14]，用加肝素抗凝和未加肝素抗凝的自体血注入到猪的额叶白质区，并分别于注血后l、4和24小时取脑组织检测发现: 未加肝素抗凝的血液在注血后l、4、24小时三个时间点上，血肿周围均产生明显的水肿； 而加肝素抗凝的血液，在上述三个时间点上，血肿周围均无水肿形成。最近，更多的研究显示^[14]: 脑内注射完整的红细胞不能引起早期的血肿周围水肿。 Gebel等^[15]也证实: 实施溶栓治疗的患者并发脑出血，其血肿周围形成的脑水肿远比自发性脑出血所诱发的脑水肿轻。Wagner等^[13]在随后的实验中证实: 在脑出血超急性期，用组织纤维溶解酶原激活剂(t-pA)注入血肿腔后行血肿吸除术，可减少血肿周围血浆蛋白及纤维蛋白的沉积，使脑水肿明显减轻，而且能预防继发性的血脑屏障破坏。这些研究表明: 血肿内血液凝固是超急性期脑出血血肿周围脑水肿形成的先决条件。凝血链锁反应的激活、血凝块的回缩(血肿形成后血块分离成一个红细胞中央块和一个血清包绕区^[6])及纤维蛋白的沉积在脑出血后血肿周围脑水肿形成中发挥着重要作用。血凝块的形成是脑实质出血血肿周围脑水肿形成的必经之步，而血浆蛋白激活(特别是凝血酶)是脑水肿形成的关键因素。

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