中国医科大学学报
中國醫科大學學報
중국의과대학학보
Journal of China Medical University
2015年
8期
694-698,703
,共6页
吴捧莲%李岩%付新慧%杜良鹤%王东玉
吳捧蓮%李巖%付新慧%杜良鶴%王東玉
오봉련%리암%부신혜%두량학%왕동옥
PJ34%金属蛋白酶9%Claudin-5%血脑屏障%缺血再灌注
PJ34%金屬蛋白酶9%Claudin-5%血腦屏障%缺血再灌註
PJ34%금속단백매9%Claudin-5%혈뇌병장%결혈재관주
PJ34%matrix metalloproteinases-9%Claudin-5%blood-brain barrier%ischemia-reperfusion
目的 探讨多聚ADP核糖聚合酶1(PARP-1)抑制剂PJ34对大鼠局灶性脑缺血再灌注后缺血侧皮层金属蛋白酶9(MMP-9)和Claudin-5表达的影响.方法 采用线栓法制备大鼠局灶脑缺血再灌注模型,腹腔注射PJ34,用伊文思蓝(EB)法检测血脑屏障通透性变化,采用2,3,5-三氨基苯甲四氮唑(TTC)染色检测脑梗死体积变化,免疫组化和western blot方法检测脑缺血侧皮层MMP-9和Claudin-5表达.结果 与假手术组比较,随缺血再灌注时间延长,模型组MMP-9表达、EB含量、脑梗死体积逐渐增加,48 h达峰;Claudin-5的表达、EB含量、脑梗死体积逐渐减少,48 h最低(P均<0.05).与模型组比较,PJ34组MMP-9表达、EB含量、脑梗死体积在各个时间点明显降低,Claudin-5的表达、EB含量、脑梗死体积在各个时间点明显增高(P均<0.05).结论PJ34通过抑制MMP-9的表达,增加Claudin-5的表达来维持血脑屏障通透性,对脑缺血再灌注损伤有神经保护作用.
目的 探討多聚ADP覈糖聚閤酶1(PARP-1)抑製劑PJ34對大鼠跼竈性腦缺血再灌註後缺血側皮層金屬蛋白酶9(MMP-9)和Claudin-5錶達的影響.方法 採用線栓法製備大鼠跼竈腦缺血再灌註模型,腹腔註射PJ34,用伊文思藍(EB)法檢測血腦屏障通透性變化,採用2,3,5-三氨基苯甲四氮唑(TTC)染色檢測腦梗死體積變化,免疫組化和western blot方法檢測腦缺血側皮層MMP-9和Claudin-5錶達.結果 與假手術組比較,隨缺血再灌註時間延長,模型組MMP-9錶達、EB含量、腦梗死體積逐漸增加,48 h達峰;Claudin-5的錶達、EB含量、腦梗死體積逐漸減少,48 h最低(P均<0.05).與模型組比較,PJ34組MMP-9錶達、EB含量、腦梗死體積在各箇時間點明顯降低,Claudin-5的錶達、EB含量、腦梗死體積在各箇時間點明顯增高(P均<0.05).結論PJ34通過抑製MMP-9的錶達,增加Claudin-5的錶達來維持血腦屏障通透性,對腦缺血再灌註損傷有神經保護作用.
목적 탐토다취ADP핵당취합매1(PARP-1)억제제PJ34대대서국조성뇌결혈재관주후결혈측피층금속단백매9(MMP-9)화Claudin-5표체적영향.방법 채용선전법제비대서국조뇌결혈재관주모형,복강주사PJ34,용이문사람(EB)법검측혈뇌병장통투성변화,채용2,3,5-삼안기분갑사담서(TTC)염색검측뇌경사체적변화,면역조화화western blot방법검측뇌결혈측피층MMP-9화Claudin-5표체.결과 여가수술조비교,수결혈재관주시간연장,모형조MMP-9표체、EB함량、뇌경사체적축점증가,48 h체봉;Claudin-5적표체、EB함량、뇌경사체적축점감소,48 h최저(P균<0.05).여모형조비교,PJ34조MMP-9표체、EB함량、뇌경사체적재각개시간점명현강저,Claudin-5적표체、EB함량、뇌경사체적재각개시간점명현증고(P균<0.05).결론PJ34통과억제MMP-9적표체,증가Claudin-5적표체래유지혈뇌병장통투성,대뇌결혈재관주손상유신경보호작용.
Objective To investigate the effects of PJ34,a poly ADP-ribose polymerase(PARP)inhibitor,on the expression of matrix metallopro-teinases-9( MMP-9 )and Claudin-5 in ischemic cortex of rats with focal cerebral ischemia-reperfusion(I/R)injury. Methods The focal cerebral ischemia-reperfusion model of middle cerebral artery occlusion(MCAO)was established by intraluminal suture . PJ34 was injected intraperitoneal-ly. Blood-brain barrier(BBB)permeability was quantitatively determined by Evans blue assay. Infarct volume changes were observed by 2,3,5-tri-phenyltetrazolium chloridedyeing(TTC)staining. The expression of the MMP-9 and Claudin-5 in rats of cerebral cortex were measured by immuno-histochemistry assay and western blot analysis . Results Compared with sham group,the expression of MMP-9,the contents of EB and infarct vol-ume increased progressively over time after I/R,and reached maximum levels at 48 h(P<0.05);The expression of Claudin-5,the contents of EB and infarct volume reduced significantly over time after I/R,and reached the minimum levels at 48 h in model group(P<0.05). Compared with model group,the expression of MMP-9,the contents of EB and infarct volume was reduced significantly and the expression of Claudin-5,the con-tents of EB and infarct volume was increased at the same time point in PJ34 group(P<0.05). Conclusion PJ34 maintained the blood-brain barri-er permeability by inhibiting the expression of MMP-9,and increasing the expression of Claudin-5,which had neuroprotection on cerebral ischemia-reperfusion injury.