乌司他丁对脑缺血再灌注大鼠脑组织中基质金属蛋白酶-9活性和细胞外基质表达的影响  

Effect of ulinastatin on the activity of matrix metalloproteinase-9 and the expression of extracellular matrix in brain tissues of rats with cerebral ische mia-reperfusion

作　　者：李青[1] 白宏英[2] 徐志秀 赵盼盼[1] 赵建华[1] 袁彬[1] 吉四辈[1] LI Qing;BAI Hongying;XU Zhixiu;ZHAO Panpan;ZHAO Jianhua;YUAN Bin;JI Sibei(Department of Neurology,the First Affiliated Hospital of Xinxiang Medical University,Henan Joint International Research Laboratory of Neurorestoratology For Senile Dementia,Weihui 453100,Henan Province,China;Department of Neurology,the Second Affiliated Hospital of Zhengzhou University,Zhengzhou 450014,Henan Province,China)

机构地区：[1]新乡医学院第一附属医院神经内科,河南省老年性痴呆神经修复国际联合实验室,河南卫辉453100 [2]郑州大学第二附属医院神经内科,河南郑州450014

出　　处：《新乡医学院学报》2020年第10期912-915,共4页Journal of Xinxiang Medical University

基　　金：河南省自然科学基金项目(编号:182300410389);新乡医学院第一附属医院青年培育基金项目(编号:QN-2019-B06)。

摘　　要：目的观察乌司他丁(UTI)对局灶性脑缺血再灌注大鼠脑组织中基质金属蛋白酶-9(MMP-9)活性、细胞外基质成分层粘连蛋白(LN)和Ⅳ型胶原(ColⅣ)表达的影响。方法采用随机数字表法将72只无特定病原级雄性Sprague Dawley大鼠分为假手术组、模型组和UTI组,每组24只。模型组和UTI组大鼠采用改进的Zea Longa线栓法制备局部脑缺血再灌注损伤模型,假手术组大鼠步骤同模型组,但不插入鱼线。缺血2 h后进行再灌注。UTI组大鼠于再灌注5 min内腹腔注射UTI(10 kU·kg^-1),每日1次,直至处死为止;模型组大鼠腹腔注射等体积的生理盐水,假手术组大鼠不给予任何干预措施。各组大鼠分别于缺血2 h再灌注6、24、48、72 h处死大鼠。采用明胶酶谱法测定大鼠缺血侧脑组织中MMP-9活性,酶联免疫吸附法检测脑组织中LN和ColⅣ水平。结果模型组和UTI组各时间点大鼠脑组织中MMP-9活性均显著高于假手术组(P<0.05),UTI组各时间点大鼠脑组织中MMP-9活性均显著低于模型组(P<0.05);模型组和UTI组各时间点大鼠脑组织中LN和ColⅣ水平均显著低于假手术组(P<0.05)。UTI组大鼠脑组织中LN和Col IV水平均显著高于模型组(P<0.05)。结论UTI可抑制大鼠脑缺血再灌注后脑组织中MMP-9活性,减少LN和ColⅣ的降解,从而减轻血脑屏障破坏,发挥脑组织保护作用。Objective To observe the effect of ulinastatin(UTI)on the activity of matrix metalloproteinase-9(MMP-9)and the expression of extracellular matrix component laminin(LN)and type IV collagen(ColⅣ)in brain tissues of rats with focal cerebral ischemia-reperfusion.Methods Seventy-two male Sprague Dawley rats without specific pathogens were randomly divided into the sham operation group,model group and UTI group,with 24 rats in each group.The rats in the model group and UTI group were made the local cerebral ischemia-reperfusion injury model by using the improved Zea Longa suture method.The procedure of the rats in the sham operation group was the same as that in the model group,but no fishing line was inserted.Rats in the UTI group were intraperitoneally injected with UTI(10 kU·kg^-1)within 5 minutes of reperfusion,once a day until sacrificed;rats in the model group were intraperitoneally injected with a corresponding volume of normal saline,and the rats in the sham operation group was not given any intervention.Rats in each group were sacrificed at reperfusion 6,24,48,72 h after ischemia for 2 h.Gelatin zymography was used to determine the activity of MMP-9 in the ischemic brain tissue of rats,and the expression levels of LN and ColⅣin the brain tissue were determined by enzyme linked immunosorbent assay.Results The activity of MMP-9 in the brain tissue of rats in the model group and UTI group at each time point was significantly higher than that in the sham operation group(P<0.05).The activity of MMP-9 in the brain tissue of rats in the UTI group was significantly lower than that in the model group at each time point(P<0.05).The levels of LN and ColⅣin the brain tissue of rats in the model group and UTI group at each time point were significantly lower than those in the sham operation group(P<0.05).The content of LN and Col IV in the brain tissue in the UTI group was significantly higher than that in the model group(P<0.05).Conclusion UTI can inhibit the activity of MMP-9 in the brain tissue of rats after cere

关 键 词：乌司他丁 脑缺血再灌注 基质金属蛋白酶-9 层粘连蛋白 Ⅳ型胶原 明胶酶谱 

分 类 号：R743.3[医药卫生—神经病学与精神病学]