国际脑血管病杂志
國際腦血管病雜誌
국제뇌혈관병잡지
INTERNATIONAL JOURNAL OF CEREBROVASCULAR DISEASES
2014年
11期
853-857
,共5页
脂氧素类%糖尿病,实验性%脑缺血%梗死,大脑中动脉%肿瘤坏死因子-α%NF-κB%炎症%大鼠
脂氧素類%糖尿病,實驗性%腦缺血%梗死,大腦中動脈%腫瘤壞死因子-α%NF-κB%炎癥%大鼠
지양소류%당뇨병,실험성%뇌결혈%경사,대뇌중동맥%종류배사인자-α%NF-κB%염증%대서
Lipoxins%Diabetes Mellitus,Experimental%Brain Ischemia%Infarction,Middle Cerebral Artery%Tumor Necrosis Factor-α%NF-κB%Inflammation%Rats
目的 探讨脂氧素A4对糖尿病大鼠脑缺血再灌注损伤的保护作用及其机制.方法 36只成年雄性Sprague-Daw ley大鼠随机分为假手术组、脑缺血再灌注组和脂氧素A4组,每组12只.应用小剂量链脲佐菌素多次腹腔注射诱发糖尿病,采用线栓法制作大脑中动脉闭塞再灌注模型.脂氧素A4组于脑缺血后5 min经侧脑室注射脂氧素A4 0.03 nmol/5μl,其余各组注射等容量生理盐水,缺血2h后拔出线栓实现再灌注.24 h时行神经功能缺损评分,然后断头取脑,2,3,5-氯化二苯四氮唑(2,3,5-triphenyl tetrazolium chloride,TTC)染色检测脑梗死面积,蛋白质印迹法检测缺血区皮质肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和核因子-κB(nuclear factor-κB,NF-κB)表达.结果 神经功能缺损评分显示,假手术组未见神经功能缺损(评分为0分),脂氧素A4组神经功能缺损评分显著低于脑缺血再灌注组[(2.20±1.03)分对(3.20±1.03)分;P<0.05].TTC染色显示,假手术组未见梗死灶,脂氧素A4组梗死面积较脑缺血再灌注组显著缩小[(27.52±5.71)%对(55.45±9.29)%;P<0.05].蛋白质印迹显示,假手术组、脑缺血再灌注组和脂氧素A4组TNF-α表达水平分别为0.64±0.16、1.85±0.52和1.40±0.34,3组间存在显著性差异(F=18.868,P<0.001),旨氧素A4组显著低于脑缺血再灌注组(P<0.05);假手术组、脑缺血再灌注组和脂氧素A4组NF-κB表达水平分别为0.79±0.24、2.09±0.47和1.27±0.35,3组间亦存在显著性差异(F=16.736,P<0.001),脂氧素A4组显著低于脑缺血再灌注组(P<0.05).结论 脂氧素A4对糖尿病大鼠局灶性脑缺血再灌注损伤具有一定的保护作用,其机制可能与抑制TNF-α和NF-κB表达有关.
目的 探討脂氧素A4對糖尿病大鼠腦缺血再灌註損傷的保護作用及其機製.方法 36隻成年雄性Sprague-Daw ley大鼠隨機分為假手術組、腦缺血再灌註組和脂氧素A4組,每組12隻.應用小劑量鏈脲佐菌素多次腹腔註射誘髮糖尿病,採用線栓法製作大腦中動脈閉塞再灌註模型.脂氧素A4組于腦缺血後5 min經側腦室註射脂氧素A4 0.03 nmol/5μl,其餘各組註射等容量生理鹽水,缺血2h後拔齣線栓實現再灌註.24 h時行神經功能缺損評分,然後斷頭取腦,2,3,5-氯化二苯四氮唑(2,3,5-triphenyl tetrazolium chloride,TTC)染色檢測腦梗死麵積,蛋白質印跡法檢測缺血區皮質腫瘤壞死因子-α(tumor necrosis factor-α,TNF-α)和覈因子-κB(nuclear factor-κB,NF-κB)錶達.結果 神經功能缺損評分顯示,假手術組未見神經功能缺損(評分為0分),脂氧素A4組神經功能缺損評分顯著低于腦缺血再灌註組[(2.20±1.03)分對(3.20±1.03)分;P<0.05].TTC染色顯示,假手術組未見梗死竈,脂氧素A4組梗死麵積較腦缺血再灌註組顯著縮小[(27.52±5.71)%對(55.45±9.29)%;P<0.05].蛋白質印跡顯示,假手術組、腦缺血再灌註組和脂氧素A4組TNF-α錶達水平分彆為0.64±0.16、1.85±0.52和1.40±0.34,3組間存在顯著性差異(F=18.868,P<0.001),旨氧素A4組顯著低于腦缺血再灌註組(P<0.05);假手術組、腦缺血再灌註組和脂氧素A4組NF-κB錶達水平分彆為0.79±0.24、2.09±0.47和1.27±0.35,3組間亦存在顯著性差異(F=16.736,P<0.001),脂氧素A4組顯著低于腦缺血再灌註組(P<0.05).結論 脂氧素A4對糖尿病大鼠跼竈性腦缺血再灌註損傷具有一定的保護作用,其機製可能與抑製TNF-α和NF-κB錶達有關.
목적 탐토지양소A4대당뇨병대서뇌결혈재관주손상적보호작용급기궤제.방법 36지성년웅성Sprague-Daw ley대서수궤분위가수술조、뇌결혈재관주조화지양소A4조,매조12지.응용소제량련뇨좌균소다차복강주사유발당뇨병,채용선전법제작대뇌중동맥폐새재관주모형.지양소A4조우뇌결혈후5 min경측뇌실주사지양소A4 0.03 nmol/5μl,기여각조주사등용량생리염수,결혈2h후발출선전실현재관주.24 h시행신경공능결손평분,연후단두취뇌,2,3,5-록화이분사담서(2,3,5-triphenyl tetrazolium chloride,TTC)염색검측뇌경사면적,단백질인적법검측결혈구피질종류배사인자-α(tumor necrosis factor-α,TNF-α)화핵인자-κB(nuclear factor-κB,NF-κB)표체.결과 신경공능결손평분현시,가수술조미견신경공능결손(평분위0분),지양소A4조신경공능결손평분현저저우뇌결혈재관주조[(2.20±1.03)분대(3.20±1.03)분;P<0.05].TTC염색현시,가수술조미견경사조,지양소A4조경사면적교뇌결혈재관주조현저축소[(27.52±5.71)%대(55.45±9.29)%;P<0.05].단백질인적현시,가수술조、뇌결혈재관주조화지양소A4조TNF-α표체수평분별위0.64±0.16、1.85±0.52화1.40±0.34,3조간존재현저성차이(F=18.868,P<0.001),지양소A4조현저저우뇌결혈재관주조(P<0.05);가수술조、뇌결혈재관주조화지양소A4조NF-κB표체수평분별위0.79±0.24、2.09±0.47화1.27±0.35,3조간역존재현저성차이(F=16.736,P<0.001),지양소A4조현저저우뇌결혈재관주조(P<0.05).결론 지양소A4대당뇨병대서국조성뇌결혈재관주손상구유일정적보호작용,기궤제가능여억제TNF-α화NF-κB표체유관.
Objective To investigate the protective effect of lipoxin A4 on diabetic rats with focal cerebral ischemia-reperfusion and its mechanisms.Methods Thirty-six adult male Sprague-Dawley rats were randomly divided into a sham operation group,a cerebral ischemia-reperfusion group,and a lipoxin A4 group (n=12 in each group).Diabetes was induced by repeated intraperitoneal injection of low-dose streptozotocin.A model of middle cerebral artery occlusion and reperfusion was induced by the intraluminal suture method.Five minutes after cerebral ischemia,lipoxin A4 0.03 nmol/5 μ1 was injected via intracerebroventricular in the lipoxin A4 group.The other groups were injected equal volume of saline.Two hours after ischemia,the suture was pulled out and reperfusion was achieved.Neurological deficit scores were performed at 24 hours.Then the rats were decapitated and their brains were taken out.2,3,5-triphenyl tetrazolium chloride (TTC) staining was used to detect infarct size.Western blotting was used to detect the expression of cortical tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB).Results The neurological deficit score showed that no neurological deficit was observed in the sham operation group (score 0).The neurological deficit score in the lipoxin A4 group was significantly lower than that in the cerebral ischemia-reperfusion group (2.20 ± 1.03 vs.3.20 ± 1.03; P <0.05).TTC staining showed that no infarct was observed in the sham operation group.The infarct size in the lipoxin A4 group was significantly lower than that in the cerebral ischemia-reperfusion group (27.52% ± 5.71% vs.55.45% ± 9.29% ; P <0.05).Western blotting showed that the expression levels of TNF-α in the sham operation,cerebral ischemiareperfusion,and lipoxin A4 groups were 0.64 ± 0.16,1.85 ± 0.52,and 1.40 ± 0.34,respectively.There were significant differences among the 3 groups (F =18.868,P <0.001).The expression level of TNF-α in the lipoxin A4 group was significantly lower than that in the cerebral ischemia-reperfusion group (P <0.05).The expression levels of NF-κB in the sham operation,cerebral ischemia-reperfusion and lipoxin A4 groups were 0.79 ±0.24,2.09 ± 0.47,and 1.27 ± 0.35,respectively.There were significant differences among the 3 groups (F =16.736,P < 0.001).The expression level of NF-κB in the lipoxin A4 group was significantly lower than that in the cerebral ischemia-reperfusion group (P <0.05).Conclusions Lipoxin A4 has certain protective effect on focal cerebral ischemia-reperfusion injury in diabetic rats,its mechanism may be associated with the inhibition of the expression of TNF-α and NF-κB.