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
709-713
,共5页
李岩%吴捧莲%杜良鹤%付新慧%王东玉
李巖%吳捧蓮%杜良鶴%付新慧%王東玉
리암%오봉련%두량학%부신혜%왕동옥
脑缺血再灌注%血脑屏障%PARP-1%PJ34%肿瘤坏死因子α%基质金属蛋白酶9
腦缺血再灌註%血腦屏障%PARP-1%PJ34%腫瘤壞死因子α%基質金屬蛋白酶9
뇌결혈재관주%혈뇌병장%PARP-1%PJ34%종류배사인자α%기질금속단백매9
ischemia-reperfusion%blood brain barrier%poly(ADP-ribose)polymerase-1%PJ34%tumor necrosis factorα%matrix metal-loproteinase 9
目的 探讨PARP-1抑制剂PJ34对大鼠局灶脑缺血再灌注损伤后血脑屏障的影响.方法 线栓法建立大鼠局灶性脑缺血再灌注模型,135只大鼠随机分为假手术组(sham组)、缺血再灌注模型组(IR组)、PJ34干预组(PJ34组),每组45只,每组大鼠再随机分为3个亚组,分别在再灌注6、24和48 h时间点处死.测定伊文思蓝(EB)含量,观察脑组织血脑屏障通透性.免疫组织化学及western bolt方法观察缺血侧皮层肿瘤坏死因子α(TNF-α)的表达和基质金属蛋白酶9(MMP-9)的活性变化.结果与sham组比较,IR组大鼠EB含量、TNF-α及MMP-9的表达明显升高(P<0.05);与IR组比较,PJ34组EB含量、TNF-α及MMP-9表达水平明显降低(P<0.05).结论 PARP-1抑制剂PJ34对大鼠脑缺血再灌注损伤后血脑屏障有一定的保护作用,其作用机制与降低缺血侧皮层TNF-α、MMP-9的表达水平,维持血脑屏障的稳定性有关.
目的 探討PARP-1抑製劑PJ34對大鼠跼竈腦缺血再灌註損傷後血腦屏障的影響.方法 線栓法建立大鼠跼竈性腦缺血再灌註模型,135隻大鼠隨機分為假手術組(sham組)、缺血再灌註模型組(IR組)、PJ34榦預組(PJ34組),每組45隻,每組大鼠再隨機分為3箇亞組,分彆在再灌註6、24和48 h時間點處死.測定伊文思藍(EB)含量,觀察腦組織血腦屏障通透性.免疫組織化學及western bolt方法觀察缺血側皮層腫瘤壞死因子α(TNF-α)的錶達和基質金屬蛋白酶9(MMP-9)的活性變化.結果與sham組比較,IR組大鼠EB含量、TNF-α及MMP-9的錶達明顯升高(P<0.05);與IR組比較,PJ34組EB含量、TNF-α及MMP-9錶達水平明顯降低(P<0.05).結論 PARP-1抑製劑PJ34對大鼠腦缺血再灌註損傷後血腦屏障有一定的保護作用,其作用機製與降低缺血側皮層TNF-α、MMP-9的錶達水平,維持血腦屏障的穩定性有關.
목적 탐토PARP-1억제제PJ34대대서국조뇌결혈재관주손상후혈뇌병장적영향.방법 선전법건립대서국조성뇌결혈재관주모형,135지대서수궤분위가수술조(sham조)、결혈재관주모형조(IR조)、PJ34간예조(PJ34조),매조45지,매조대서재수궤분위3개아조,분별재재관주6、24화48 h시간점처사.측정이문사람(EB)함량,관찰뇌조직혈뇌병장통투성.면역조직화학급western bolt방법관찰결혈측피층종류배사인자α(TNF-α)적표체화기질금속단백매9(MMP-9)적활성변화.결과여sham조비교,IR조대서EB함량、TNF-α급MMP-9적표체명현승고(P<0.05);여IR조비교,PJ34조EB함량、TNF-α급MMP-9표체수평명현강저(P<0.05).결론 PARP-1억제제PJ34대대서뇌결혈재관주손상후혈뇌병장유일정적보호작용,기작용궤제여강저결혈측피층TNF-α、MMP-9적표체수평,유지혈뇌병장적은정성유관.
Objective To investigate the influence of poly(ADP-ribose)polymerase inhibitor PJ34 on blood brain barrier(BBB)in rats with cere-bral ischemia-reperfusion injury. Methods Rat model of cerebral ischemia-reperfusion injury was established by the middle cerebral artery occlu-sion. A total of 135 SD rats were randomly divided into 3 groups:sham-operated group(sham group),ischemia-reperfusion group(IR group)and PJ34 group(PJ34 group). 45 animals in each group were then equally divided into subgroups and the rats were sacrificed at 6 h,24 h,48 h after re-perfusion,respectively. BBB permeability was evaluated by detection of extravasated Evans blue(EB). The expression of tumor necrosis factorα(TNF-α)and matrix metalloproteinase 9(MMP-9)activity were measured by immunohistochemistry and western blot at different time points. Re?sults Compared with sham group,the contents of EB and the expressions of TNF-αand MMP-9 in IR group were increased significantly(P<0.05). Compared with IR group,the contents of EB and the expressions of TNF-αand MMP-9 in PJ34 group were markedly decreased at the same time point(P<0.05). Conclusion The present study provided in vivo evidence that PARP inhibitor PJ34 can protect against cerebral ischemia re-perfusion injury,and the mechanism might be related to maintaining the stability of blood-brain barrier by suppressing the expression of TNF-αand MMP-9 in ischemic cortex.
