医学研究生学报
醫學研究生學報
의학연구생학보
JOURNAL OF MEDICAL POSTGRADUATE
2014年
11期
1128-1132
,共5页
李桃%王汉东%丁宇%何进%丁可%陆新宇%徐建国
李桃%王漢東%丁宇%何進%丁可%陸新宇%徐建國
리도%왕한동%정우%하진%정가%륙신우%서건국
核因子E2相关因子2%蛛网膜下腔出血%氧化应激%炎症因子%早期脑损伤%脑血管痉挛
覈因子E2相關因子2%蛛網膜下腔齣血%氧化應激%炎癥因子%早期腦損傷%腦血管痙攣
핵인자E2상관인자2%주망막하강출혈%양화응격%염증인자%조기뇌손상%뇌혈관경련
NF-E2-related factor 2%Subarachnoid hemorrhage%Oxidative stress%Inflammatory factor%Early brain injury%Cerebral vasospasm
目的:蛛网膜下腔出血( subarachnoid hemorrhage, SAH)是一种致死率较高的危重疾病,文中研究氧化应激调节因子Nrf2在SAH后脑损伤作用及机制。方法实验选取雄性ICR野生型( wild type, WT)小鼠及来源于ICR的Nrf2基因敲除( knockout, KO)小鼠,采用视交叉自体血注射建立小鼠SAH模型,实验动物分为WT假手术组、KO假手术组、WT SAH组和KO SAH组4个组,检测SAH后24 h氧化应激产物丙二醛( malondialdehyde, MDA)及GSH/GSSG,炎症因子TNF-α和IL-1β,脑组织含水量和伊文思蓝含量,TUNEL和尼氏染色,活动评分及大脑前和大脑中动脉血管痉挛情况。结果与假手术组比较,SAH组MDA、TNF-α、IL-1β表达量上升,而GSH/GSSG下降( P<0.01);与WT SAH组比较,MDA、TNF-α、IL-1β表达量上升(P<0.05),而GSH/GSSG下降(P<0.05)。 SAH组前脑脑组织含水量、伊文思蓝含量较假手术组增加(P<0.01),与WT SAH组比较,KO SAH组脑组织含水量、伊文思蓝含量均升高[(0.808±0.004) vs (0.819±0.004)、(7.230±1.192)μg/g vs (11.628±1.040)μg/g, P<0.05]。 SAH后24 h,与假手术组比较,SAH组神经细胞凋亡率上升(P<0.01),而神经元数量、ACA比值、血管半径/壁厚值、活动评分下降(P<0.01),与WT SAH组比较,KO SAH组细胞凋亡率上升[(23.733±8.204)%vs (36.267±10.612)%],而神经元数、ACA比值、血管半径/壁厚值、活动评分下降[(70.833±8.750) vs (51.767±13.006),(8.024±2.780) vs (6.861±2.702),(6.337±3.993) vs (5.107±38.05),(1.967±0.928)v s (1.433±0.679), P<0.05]。结论 N rf2 KO加重了SAH后氧化应激和炎性反应,从而导致了SAH继发性脑损伤加重。 Nrf2对SAH 后继发性脑损伤具有保护作用。
目的:蛛網膜下腔齣血( subarachnoid hemorrhage, SAH)是一種緻死率較高的危重疾病,文中研究氧化應激調節因子Nrf2在SAH後腦損傷作用及機製。方法實驗選取雄性ICR野生型( wild type, WT)小鼠及來源于ICR的Nrf2基因敲除( knockout, KO)小鼠,採用視交扠自體血註射建立小鼠SAH模型,實驗動物分為WT假手術組、KO假手術組、WT SAH組和KO SAH組4箇組,檢測SAH後24 h氧化應激產物丙二醛( malondialdehyde, MDA)及GSH/GSSG,炎癥因子TNF-α和IL-1β,腦組織含水量和伊文思藍含量,TUNEL和尼氏染色,活動評分及大腦前和大腦中動脈血管痙攣情況。結果與假手術組比較,SAH組MDA、TNF-α、IL-1β錶達量上升,而GSH/GSSG下降( P<0.01);與WT SAH組比較,MDA、TNF-α、IL-1β錶達量上升(P<0.05),而GSH/GSSG下降(P<0.05)。 SAH組前腦腦組織含水量、伊文思藍含量較假手術組增加(P<0.01),與WT SAH組比較,KO SAH組腦組織含水量、伊文思藍含量均升高[(0.808±0.004) vs (0.819±0.004)、(7.230±1.192)μg/g vs (11.628±1.040)μg/g, P<0.05]。 SAH後24 h,與假手術組比較,SAH組神經細胞凋亡率上升(P<0.01),而神經元數量、ACA比值、血管半徑/壁厚值、活動評分下降(P<0.01),與WT SAH組比較,KO SAH組細胞凋亡率上升[(23.733±8.204)%vs (36.267±10.612)%],而神經元數、ACA比值、血管半徑/壁厚值、活動評分下降[(70.833±8.750) vs (51.767±13.006),(8.024±2.780) vs (6.861±2.702),(6.337±3.993) vs (5.107±38.05),(1.967±0.928)v s (1.433±0.679), P<0.05]。結論 N rf2 KO加重瞭SAH後氧化應激和炎性反應,從而導緻瞭SAH繼髮性腦損傷加重。 Nrf2對SAH 後繼髮性腦損傷具有保護作用。
목적:주망막하강출혈( subarachnoid hemorrhage, SAH)시일충치사솔교고적위중질병,문중연구양화응격조절인자Nrf2재SAH후뇌손상작용급궤제。방법실험선취웅성ICR야생형( wild type, WT)소서급래원우ICR적Nrf2기인고제( knockout, KO)소서,채용시교차자체혈주사건립소서SAH모형,실험동물분위WT가수술조、KO가수술조、WT SAH조화KO SAH조4개조,검측SAH후24 h양화응격산물병이철( malondialdehyde, MDA)급GSH/GSSG,염증인자TNF-α화IL-1β,뇌조직함수량화이문사람함량,TUNEL화니씨염색,활동평분급대뇌전화대뇌중동맥혈관경련정황。결과여가수술조비교,SAH조MDA、TNF-α、IL-1β표체량상승,이GSH/GSSG하강( P<0.01);여WT SAH조비교,MDA、TNF-α、IL-1β표체량상승(P<0.05),이GSH/GSSG하강(P<0.05)。 SAH조전뇌뇌조직함수량、이문사람함량교가수술조증가(P<0.01),여WT SAH조비교,KO SAH조뇌조직함수량、이문사람함량균승고[(0.808±0.004) vs (0.819±0.004)、(7.230±1.192)μg/g vs (11.628±1.040)μg/g, P<0.05]。 SAH후24 h,여가수술조비교,SAH조신경세포조망솔상승(P<0.01),이신경원수량、ACA비치、혈관반경/벽후치、활동평분하강(P<0.01),여WT SAH조비교,KO SAH조세포조망솔상승[(23.733±8.204)%vs (36.267±10.612)%],이신경원수、ACA비치、혈관반경/벽후치、활동평분하강[(70.833±8.750) vs (51.767±13.006),(8.024±2.780) vs (6.861±2.702),(6.337±3.993) vs (5.107±38.05),(1.967±0.928)v s (1.433±0.679), P<0.05]。결론 N rf2 KO가중료SAH후양화응격화염성반응,종이도치료SAH계발성뇌손상가중。 Nrf2대SAH 후계발성뇌손상구유보호작용。
Objective Subarachnoid hemorrhage ( SAH) is a devastating disease with a high mortality.This study was to in-vestigate the effect of Nrf2 on secondary brain injury following SAH and its action mechanism in mice. Methods SAH models were established in wild-type ( WT) and Nrf2 knockout ( KO) ICR male mice by injecting fresh blood drawn from the femoral artery into the pre-chiasmatic cistern.The animals were divided into four groups, WT sham, WT SAH, KO sham, and KO SAH.At 24 hours after modeling, the expression levels of malondialdehyde ( MDA) , GSH/GSSG, TNF-αand IL-1β, the volume of brain water, and content of Evans blue were measured, the activity scores obtained, and cerebral vasospasm of the anterior and middle cerebral arteries ( ACA and MCA) detected. Results At 24 hours, the expressions of MDA, TNF-α, and IL-1βwere (3.299 ±0.335), (1.187 ± 0.436), and (59.330 ±21.787) mg/g in the WT sham group, (4.339 ±0.328), (2.432 ±0.434), and (121.584 ±21.675) mg/g in the WT SAH group, (3.488 ±0.634), (1.170 ±0.312), and (58.497 ±15.608) mg/g in the KO sham group, and (5.335 ±0.499), (3.132 ±0.548), and (171.117 ±50.479) mg/g in the KO SAH group, markedly increased in the SAH groups as compared with the sham controls (P<0.05), while the GSH/GSSG levels were significantly higher in the former two groups than in the latter (0.553 ±0.100 and 0.375 ±0.068 vs 0.714 ±0.091, 0.761 ±0.114, P<0.01).The contents of brain water and Evans blue were (0.784 ±0.005) and (7.055 ±1.046) μg/g in the WT sham group, (0.808 ±0.004) and (7.230 ±1.192) μg/g in the WT SAH group, (0.784 ±0.004) and (9.620 ±1.290) μg/g in the KO sham group, and (0.819 ±0.004) and (11.628 ±1.040)μg/g in the KO SAH group, remarkably increased in the SAH groups in comparison with the sham groups (P<0.05).The apoptosis rate 8.916 and 82.100 ±6.870 vs 70.833 ±8.750 and 51.767 ±13.006), ACA radius/wall thickness value (13.885 ±3.360 and 14.212 ±3.2545 vs 8.024 ±2.780 and 6.861 ±2.702), MCA radius/wall thickness value (18.648 ±2.893 and 19.435 ±2.775 vs 6.337 ±3.993 and 5.107 ±3.805), and activity score (2.733 ±0.450 and 2.767 ±0.430 vs 1.967 ±0.928 and 1.433 ±0.679) (all P<0.01). Conclusion Nrf2 knockout increases oxidative stress and inflammatory reaction following SAH and consequently aggravates secondary brain injury.Nrf2 has a protective effect against SAH-induced brain injury.