中华创伤杂志
中華創傷雜誌
중화창상잡지
Chinese Journal of Traumatology
2014年
12期
1230-1235
,共6页
陶晓刚%刘佰运%陈学涛%郝淑煜%田润发
陶曉剛%劉佰運%陳學濤%郝淑煜%田潤髮
도효강%류백운%진학도%학숙욱%전윤발
脑损伤%血脑屏障%基质金属蛋白酶-9%多聚腺苷二磷酸-核糖聚合酶
腦損傷%血腦屏障%基質金屬蛋白酶-9%多聚腺苷二燐痠-覈糖聚閤酶
뇌손상%혈뇌병장%기질금속단백매-9%다취선감이린산-핵당취합매
Brain injuries%Blood-brain barrier%Matrix metalloproteinase 9%Poly(ADP-ribose) polymerase
目的 探讨多聚腺苷二磷酸-核糖聚合酶[poly(ADP-ribose)polymerase,PARP]抑制剂P J34对小鼠创伤性脑损伤(traumatic brain injury,TBI)后血脑屏障(blood-brain barrier,BBB)通透性及脑组织中基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)表达变化的影响.方法 健康成年BALB/c雄性小鼠136只,按随机数字表法分为假手术组、损伤组和PARP抑制剂(PJ34)组,建立小鼠可控性皮质打击伤模型.在伤后6,24 h时,从运动、感觉、反射和平衡等方面评价小鼠的神经功能缺损;伊文思蓝法测定BBB通透性变化和干湿重法测定脑组织含水量;采用HE染色测定损伤体积,评价损伤脑区神经元的死亡;免疫印迹方法测定MMP-9的表达量.结果 (1)与损伤组[12.50±0.39、11.80±0.32、(25.37±1.75) mm3、(28.24±1.51)mm3]比较,P J34组[8.00±0.26、7.50±0.25、(11.25±0.91)mm3、(13.55±1.06) mm3]神经功能评分、脑挫裂伤体积在伤后6h和24 h均明显降低(P＜0.01);(2)与损伤组[(936.96±4.71) μg/mg、(1 302.23-±5.89) μg/mg]比较,PJ34组[(440.08±3.10) μg/mg、(860.46±3.86) μg/mg] BBB通透性在伤后6 h和24 h明显降低(P＜0.01),脑含水量PJ34组在伤后6h较损伤组显著降低[(82.55±0.73)％∶(80.77±0.76)％](P＜0.01),但在伤后24 h无明显差异;(3)在伤后6h和24 h,MMP-9的表达H34组均低于损伤组(P＜0.05或0.01) .结论 PARP抑制剂PJ34可下调小鼠TBI后MMP-9的高表达,减轻BBB通透性破坏,从而起到脑保护作用.
目的 探討多聚腺苷二燐痠-覈糖聚閤酶[poly(ADP-ribose)polymerase,PARP]抑製劑P J34對小鼠創傷性腦損傷(traumatic brain injury,TBI)後血腦屏障(blood-brain barrier,BBB)通透性及腦組織中基質金屬蛋白酶-9(matrix metalloproteinases-9,MMP-9)錶達變化的影響.方法 健康成年BALB/c雄性小鼠136隻,按隨機數字錶法分為假手術組、損傷組和PARP抑製劑(PJ34)組,建立小鼠可控性皮質打擊傷模型.在傷後6,24 h時,從運動、感覺、反射和平衡等方麵評價小鼠的神經功能缺損;伊文思藍法測定BBB通透性變化和榦濕重法測定腦組織含水量;採用HE染色測定損傷體積,評價損傷腦區神經元的死亡;免疫印跡方法測定MMP-9的錶達量.結果 (1)與損傷組[12.50±0.39、11.80±0.32、(25.37±1.75) mm3、(28.24±1.51)mm3]比較,P J34組[8.00±0.26、7.50±0.25、(11.25±0.91)mm3、(13.55±1.06) mm3]神經功能評分、腦挫裂傷體積在傷後6h和24 h均明顯降低(P＜0.01);(2)與損傷組[(936.96±4.71) μg/mg、(1 302.23-±5.89) μg/mg]比較,PJ34組[(440.08±3.10) μg/mg、(860.46±3.86) μg/mg] BBB通透性在傷後6 h和24 h明顯降低(P＜0.01),腦含水量PJ34組在傷後6h較損傷組顯著降低[(82.55±0.73)％∶(80.77±0.76)％](P＜0.01),但在傷後24 h無明顯差異;(3)在傷後6h和24 h,MMP-9的錶達H34組均低于損傷組(P＜0.05或0.01) .結論 PARP抑製劑PJ34可下調小鼠TBI後MMP-9的高錶達,減輕BBB通透性破壞,從而起到腦保護作用.
목적 탐토다취선감이린산-핵당취합매[poly(ADP-ribose)polymerase,PARP]억제제P J34대소서창상성뇌손상(traumatic brain injury,TBI)후혈뇌병장(blood-brain barrier,BBB)통투성급뇌조직중기질금속단백매-9(matrix metalloproteinases-9,MMP-9)표체변화적영향.방법 건강성년BALB/c웅성소서136지,안수궤수자표법분위가수술조、손상조화PARP억제제(PJ34)조,건립소서가공성피질타격상모형.재상후6,24 h시,종운동、감각、반사화평형등방면평개소서적신경공능결손;이문사람법측정BBB통투성변화화간습중법측정뇌조직함수량;채용HE염색측정손상체적,평개손상뇌구신경원적사망;면역인적방법측정MMP-9적표체량.결과 (1)여손상조[12.50±0.39、11.80±0.32、(25.37±1.75) mm3、(28.24±1.51)mm3]비교,P J34조[8.00±0.26、7.50±0.25、(11.25±0.91)mm3、(13.55±1.06) mm3]신경공능평분、뇌좌렬상체적재상후6h화24 h균명현강저(P＜0.01);(2)여손상조[(936.96±4.71) μg/mg、(1 302.23-±5.89) μg/mg]비교,PJ34조[(440.08±3.10) μg/mg、(860.46±3.86) μg/mg] BBB통투성재상후6 h화24 h명현강저(P＜0.01),뇌함수량PJ34조재상후6h교손상조현저강저[(82.55±0.73)％∶(80.77±0.76)％](P＜0.01),단재상후24 h무명현차이;(3)재상후6h화24 h,MMP-9적표체H34조균저우손상조(P＜0.05혹0.01) .결론 PARP억제제PJ34가하조소서TBI후MMP-9적고표체,감경BBB통투성파배,종이기도뇌보호작용.
Objective To investigate the role of poly(ADP-ribose) polymerase (PARP) inhibitor PJ34 in regulating blood-brain barrier (BBB) permeability and matrix metalloproteinases-9 (MMP-9) expression in a mouse model of traumatic brain injury (TBI).Methods A total of 136 adult male BALB/c mice were randomly divided into sham-operated group,injured group and PJ34-treated group according to the random number table.Controlled cortical impact in mice was established.At 6 and 24hours postinjury,neurological deficit was evaluated,including motor,sensory,reflex and beam balance tests ; BBB permeability and brain water content were detected using Evans blue test and gravimetric technique; brain contusion volume was measured using HE staining; levels of MMP-9 in cytosolic fractions were detected using Western blotting.Results At 6 and 24 hours postinjury,neurological severity score in PJ34-treated group (8.00 ± 0.26,7.50 ±0.25) were lower than those in injured group (12.50 ±0.39,11.80 ± 0.32) ; brain contusion volume in PJ34-treated group [(11.25 ± 0.91) mm3,(13.55 ±1.06) mm3] was lower than those in injured group [(25.37 ± 1.75) mm3,(28.24 ± 1.51) mm3] ; BBB permeability in PJ34-treated group [(440.08 ± 3.10) μg/mg,(860.46 ± 3.86) μg/mg] was lower than those in injured group [(936.96 ± 4.71) μg/mg,(1 302.23 ± 5.89) μg/mg] (all P ＜ 0.01).Brain water content lowered significantly in PJ34-treated group than in injured group at 6 hours postinjury [(80.77 ± 0.76) ％ vs (82.55 ± 0.73) ％,P ＜ 0.0l],but between-group difference was not significant at 24 hours postinjury.Lower levels in MMP-9 were also observed in PJ34-treated group compared with injured group at 6 and 24 hours postinjury(P ＜ 0.05 or 0.01).Conclusion PARP inhibitor PJ34 can attenuate MMP-9 up-regulation,inhibit BBB injury and hence protect the brain against TBI in mice.
