摘要
目的 研究老年脑缺血/再灌注(I/R)不同时期微血管基底膜损伤与明胶酶系的关系.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,将大鼠分为青年组和老龄组,各组又分为假手术组、制模后缺血(1)3 h和I/R 6 h、12 h、24 h、3 d、6 d时间点组.采用免疫组化和酶谱分析方法测定脑微血管结构、基底膜Ⅳ型胶原(Col Ⅳ)、层连蛋白(LN)和基质金属蛋白酶(MMPs)及其抑制剂(TIMPs)的变化.结果 与青年假手术组比较.老龄假手术组Col IV、LN升高和MMP-2、MMP-9表达增强.随I/R时间的延长,老龄与青年大鼠摹底膜成分Col IV和LN表达递减;MMP-2表达递增,MMP-9、TIMP-1表达呈先增强而后降低趋势.与青年模型组相同时间点比较,老龄模型组Col IV(I 3 h、1/R 6 h、I/R 12 h)、LN(1 3 h、I/R 6～24 h)、MMP-2(I 3 h,I/R 6 h～6 d)、MMP-9(I 3 h、1/R 6～24 h)表达水平增强,TIMP-1(I/R 24 h)表达水平降低,差异均有统计学意义(P＜0.05或P＜0.01).各组MMP-2与MMP-9的酶谱分析比较,量的变化与免疫表达规律基本一致.结论 随着增龄,大鼠腩微血管基底膜成分改变与MMPs、TIMP的变化有关.在脑I/R脑微血管基底膜损伤方面,老龄大鼠较青年严重,其损伤的特点与明胶酶系变化有关.
Objective To study the relationship of cerebro-microvessel basement membrane injury and gelatinase system after cerebral ischemia/reperfusion(I/R)in aged rats.Methods Cerebral I/R injury model was reproduced by intraluminal silk ligature thrombosis of the middle cerebral artery occlusion (MCAO).Rats were divided randomly into sham control and I/R groups in young rats Cischemia 3 hours (13 h)and reperfusion 6 hours(I/R 6 h),12 hours(1/R 12 h),24 hours(I/R 24 h),3 days(1/R 3 d),6 days(I/R 6 d)],and sham control group and I/R group in aged rats(1 3 h and I/R 6 h,I/R 12 h,I/R 24 h,1/R 3 d,1/R 6 d).The change in cerebro-cortex microvessel basement membrane structure,basement membrane type Ⅳ collagen(Col Ⅳ)and laminin(LN)contents,matrix metalloproteinases(MMPs)and tissue inhibitor of metalloproteinases(TIMPs)expression in every group were determined with immunohis tochemical method and zymogram analysis.Results With the inerease in age,Col Ⅳ and LN contents of the microvessel basement membrane were increased,and MMP-2 and MMP-9 expressions were stronger.With prolongation of I/R.the degradation of microvessel basement membrane components(Col Ⅳ and LN)was positively correlated with the duration of cerebral I/R.MMP-2 expression was increased gradually,and MMP-9 and TIMP-1 expression increased at the beginning and decreased subsequently.Col Ⅳ(I 3 h,I/R 6 h,I/R 12 h),LN(1 3 h,I/R 6-24 h),MMP-2(I 3 h,1/R 6 h-6 d)and MMP-9(1 3 h,I/R 6-24 h)expression level in aged rats with I/R injury were higher,and TIMP-1(I/R 24 h)expression was lower than those in young rats(P＜0.05 or P＜0.01).In addition,changes in MMP-2 and MMP-9 contents as determined by zymogram analysis method coincided with their immunoexpression.Conclusion With the increase of age,alteration in membrane components of eerebro-microvessel basement membrane in rats is related with MMPs and TlMP.Cerebro-mierovesseI basement membrane injury is more serious in aged rats than that of young rats.Changes in cerebro-microvessel basement membrane injury in aged ra
出处
《中华危重病急救医学》
CAS
CSCD
北大核心
2008年第11期-,共4页
Chinese Critical Care Medicine
基金
国家自然科学基金，河南省杰出青年科学基金
