老龄大鼠脑缺血-再灌注微血管基底膜损伤变化及与纤溶酶原激活系的关系  

Relationship of changes in basement membrane of microvessels after cerebral ischemia/reperfusion and plasminogen activator system in aged rats

作　　者：刘轲[1] 李建生[1] 王明航[1] 刘敬霞[1] 赵跃武[1] 刘振国[1] 

机构地区：[1]河南中医学院老年医学研究所,郑州450003

出　　处：《中国危重病急救医学》2005年第11期654-657,共4页Chinese Critical Care Medicine

基　　金：国家自然科学基金资助项目(30371812);河南省高校创新人才基金项目(200010)

摘　　要：目的研究老龄大鼠脑缺血再灌注(I/R)不同时期微血管基底膜损伤与纤溶酶原激活系的关系。方法采用大脑中动脉阻塞(MCAO)线栓法制备大鼠局灶性脑I/R模型,将大鼠分为青年假手术组、老龄假手术组、青年模型组和老龄模型组,其中模型组又分为I3h,I/R6、12、24、72和144h各时间点组。采用免疫组化、酶谱与反向酶谱分析等方法测定各脑微血管结构、基底膜型胶原、层连蛋白(LN)和纤溶酶原激活系的变化。结果与青年假手术组比较,老龄假手术组型胶原、LN表达增强。随着I/R时间的延长,老龄与青年大鼠基底膜成分型胶原和LN表达递减;组织型纤溶酶原激活剂(tPA)、尿激酶型纤溶酶原激活剂(uPA)、纤溶酶原激活物抑制剂(PAI1)表达水平呈先增强后降低的趋势。与青年模型组相同时间点比较,老龄模型组型胶原(I3h、I/R6h、I/R12h)、LN(I3h、I/R6h^24h)、tPA(I/R6h^24h)、uPA(I/R12h^144h)表达增强,PAI1(I/R12h、I/R24h)表达降低,差异均有显著性。另外,PAI1的反向酶谱分析比较,量的变化与免疫表达规律基本一致。结论随着增龄,大鼠脑微血管基底膜成分型胶原、LN增加。在脑I/R微血管基底膜损伤方面,老龄大鼠较青年严重,其损伤的特点与纤溶酶原激活系变化有关。Objective To study the relationship o[ changes in basement membrane of cerebral microvessels and plasminogen activator system after cerebral ischemia/reperfusion （I/R） iniury in aged rats. Methods Middle cerebral artery occlusion （MCAO） was produced by the introduction of a thread. Rats were divided randomly into sham -operation group with young rats （cerebral ischemia 3 hours and I/R 6, 12, 24, 72, 144 hours groups）, sham -operation group and I/R groups in aged rats （cerebral ischemia 3 hours and I/R 6, 12, 24, 72, 144 hours groups）. Immunohistochemical technique, zymogram analysis, and reverse zymogram analysis were used to study changes in basement membrane structure of cerebral-cortex microvessel, type N collagen （Col Ⅳ ） and laminine （LN） contents, and plasminogen activator system in every group. Results With the increase of age, Col N and LN contents of the microvessel basement membrane increased. With prolongation of I/R, the contents of Col N and LN decreased in both young and aged rats, while the contents of tissue plasminogen activator （t -PA）, urokinase plasminogen （u-PA） and plasminogen activator inhibitor （PAI- 1） expression increased at the beginning and decreased subsequently. Compared with young groups, Col N （ischemia 3 hours- I/R 12 hours）, LN （ischemia 3 hours-I/R 24 hours）, t -PA （I/R 6- 24 hours） and u -PA （I/R 12 -144 hours） expression levels were higher in aged rats, but PAI- 1 （I/R 12 and 24 hours） expression was lower. In addition, changes in PAI- 1 contents as determined with reverse zymogram analysis method coincided with its immunoexpression. Conclusion With the increase of age, alterations in constitutents of cerebro - microvessel basement membrane （Col N and LN） increased. Injury to cerebro -microvessel basement membrane resulted in more serious changes in aged rats combared with the young rats. Changes in cerebro -microvessel basement membrane alter I/R injury in the aged SD rats is related to change in plasminogen activa

关 键 词：老龄 大鼠 缺血-再灌注 脑 微血管基底膜 细胞外基质 纤溶酶原激活系 

分 类 号：R743[医药卫生—神经病学与精神病学]