国际脑血管病杂志
國際腦血管病雜誌
국제뇌혈관병잡지
INTERNATIONAL JOURNAL OF CEREBROVASCULAR DISEASES
2012年
9期
690-695
,共6页
党辉%艾山江%补娟%李健%沙晶%景燕%地力木拉提%阿斯亚%朱沂
黨輝%艾山江%補娟%李健%沙晶%景燕%地力木拉提%阿斯亞%硃沂
당휘%애산강%보연%리건%사정%경연%지력목랍제%아사아%주기
脑缺血%再灌注%Toll样受体4%NF-κB%天山雪莲%神经保护药%疾病模型,动物%小鼠
腦缺血%再灌註%Toll樣受體4%NF-κB%天山雪蓮%神經保護藥%疾病模型,動物%小鼠
뇌결혈%재관주%Toll양수체4%NF-κB%천산설련%신경보호약%질병모형,동물%소서
Brain Ischemia%Reperfusion Injury%Toll-Like Receptor 4%NF-κB%Herba Saussureae Involucratae%Neuroprotective Agents%Disease Models,Animal%Mice
目的 探讨雪莲提取物预处理对脑缺血再灌注小鼠脑组织Toll样受体4(Toll like receptor 4,TLR4)和核因子-κB(nuclear factor-κB,NF-κB)表达的影响及其可能的神经保护机制.方法 72只昆明小鼠随机分为假手术组、生理盐水组、雪莲提取物组以及依达拉奉组,每组18只.雪莲提取物组经腹腔给予雪莲注射液0.8 g/kg,依达拉奉组给予依达拉奉3 mg/kg,生理盐水组给予同体积生理盐水.连续给药7d后制作大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型,应用2,3,5-氯化三苯基四氮唑染色测定脑梗死体积,应用免疫组织化学染色法检测缺血脑组织TLR4阳性细胞,逆转录聚合酶链反应检测TLR4和NF-κB mRNA表达.结果 生理盐水组、雪莲提取物组和依达拉奉组小鼠脑梗死体积分别为(131.55 ±28.25)mm3、(84.10±13.92)mm3和(65.10±6.78)mm3,存在显著性差异(F=10.158,P=0.012).雪莲提取物组(P =0.020)和依达拉奉组(P=0.005)梗死体积均显著小于生理盐水组,而雪莲提取物组与依达拉奉组无显著性差异.生理盐水组缺血侧皮质和海马区TLR4阳性细胞数显著多于假手术组(P均＜0.001),雪莲提取物组和依达拉奉组皮质和海马TLR4阳性细胞数均显著少于生理盐水组(P均＜0.05),而雪莲提取物组与依达拉奉组无显著差异.生理盐水组TLR4、p50和p65 mRNA表达均较假手术组显著上调(P均为0.000).雪莲提取物能显著下调缺血再灌注24 h时的TLR4、p50和p65 mRNA表达(P均为0.000)；依达拉奉能显著下调TLR4和p65 mRNA表达(P均为0.000),对p50 mRNA表达有下调趋势(P=0.053)；而雪莲提取物组与依达拉奉组之间TLR4和p65 mRNA表达均无显著性差异.结论 雪莲提取物预处理能显著缩小脑梗死体积,下调TLR4和NF-κB亚基表达,通过抑制缺血后炎症反应发挥神经保护作用.
目的 探討雪蓮提取物預處理對腦缺血再灌註小鼠腦組織Toll樣受體4(Toll like receptor 4,TLR4)和覈因子-κB(nuclear factor-κB,NF-κB)錶達的影響及其可能的神經保護機製.方法 72隻昆明小鼠隨機分為假手術組、生理鹽水組、雪蓮提取物組以及依達拉奉組,每組18隻.雪蓮提取物組經腹腔給予雪蓮註射液0.8 g/kg,依達拉奉組給予依達拉奉3 mg/kg,生理鹽水組給予同體積生理鹽水.連續給藥7d後製作大腦中動脈閉塞(middle cerebral artery occlusion,MCAO)模型,應用2,3,5-氯化三苯基四氮唑染色測定腦梗死體積,應用免疫組織化學染色法檢測缺血腦組織TLR4暘性細胞,逆轉錄聚閤酶鏈反應檢測TLR4和NF-κB mRNA錶達.結果 生理鹽水組、雪蓮提取物組和依達拉奉組小鼠腦梗死體積分彆為(131.55 ±28.25)mm3、(84.10±13.92)mm3和(65.10±6.78)mm3,存在顯著性差異(F=10.158,P=0.012).雪蓮提取物組(P =0.020)和依達拉奉組(P=0.005)梗死體積均顯著小于生理鹽水組,而雪蓮提取物組與依達拉奉組無顯著性差異.生理鹽水組缺血側皮質和海馬區TLR4暘性細胞數顯著多于假手術組(P均＜0.001),雪蓮提取物組和依達拉奉組皮質和海馬TLR4暘性細胞數均顯著少于生理鹽水組(P均＜0.05),而雪蓮提取物組與依達拉奉組無顯著差異.生理鹽水組TLR4、p50和p65 mRNA錶達均較假手術組顯著上調(P均為0.000).雪蓮提取物能顯著下調缺血再灌註24 h時的TLR4、p50和p65 mRNA錶達(P均為0.000)；依達拉奉能顯著下調TLR4和p65 mRNA錶達(P均為0.000),對p50 mRNA錶達有下調趨勢(P=0.053)；而雪蓮提取物組與依達拉奉組之間TLR4和p65 mRNA錶達均無顯著性差異.結論 雪蓮提取物預處理能顯著縮小腦梗死體積,下調TLR4和NF-κB亞基錶達,通過抑製缺血後炎癥反應髮揮神經保護作用.
목적 탐토설련제취물예처리대뇌결혈재관주소서뇌조직Toll양수체4(Toll like receptor 4,TLR4)화핵인자-κB(nuclear factor-κB,NF-κB)표체적영향급기가능적신경보호궤제.방법 72지곤명소서수궤분위가수술조、생리염수조、설련제취물조이급의체랍봉조,매조18지.설련제취물조경복강급여설련주사액0.8 g/kg,의체랍봉조급여의체랍봉3 mg/kg,생리염수조급여동체적생리염수.련속급약7d후제작대뇌중동맥폐새(middle cerebral artery occlusion,MCAO)모형,응용2,3,5-록화삼분기사담서염색측정뇌경사체적,응용면역조직화학염색법검측결혈뇌조직TLR4양성세포,역전록취합매련반응검측TLR4화NF-κB mRNA표체.결과 생리염수조、설련제취물조화의체랍봉조소서뇌경사체적분별위(131.55 ±28.25)mm3、(84.10±13.92)mm3화(65.10±6.78)mm3,존재현저성차이(F=10.158,P=0.012).설련제취물조(P =0.020)화의체랍봉조(P=0.005)경사체적균현저소우생리염수조,이설련제취물조여의체랍봉조무현저성차이.생리염수조결혈측피질화해마구TLR4양성세포수현저다우가수술조(P균＜0.001),설련제취물조화의체랍봉조피질화해마TLR4양성세포수균현저소우생리염수조(P균＜0.05),이설련제취물조여의체랍봉조무현저차이.생리염수조TLR4、p50화p65 mRNA표체균교가수술조현저상조(P균위0.000).설련제취물능현저하조결혈재관주24 h시적TLR4、p50화p65 mRNA표체(P균위0.000)；의체랍봉능현저하조TLR4화p65 mRNA표체(P균위0.000),대p50 mRNA표체유하조추세(P=0.053)；이설련제취물조여의체랍봉조지간TLR4화p65 mRNA표체균무현저성차이.결론 설련제취물예처리능현저축소뇌경사체적,하조TLR4화NF-κB아기표체,통과억제결혈후염증반응발휘신경보호작용.
Objective To investigate the effects of Saussurea involucrata extract pretreatment on the expression of the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) in focal cerebral ischemia/reperfusion in mice and its possible neuroprotective mechanism.Methods Seventy-two Kunming mice were randomly divided into four groups:sham operation,saline,Saussurea involucrata extract,and edaravone groups (n =18 in each group).Saussurea involucrata extract 0.8 g/kg was given intraperitoneally in the Saussurea involucrata extract group; edaravone 3 mg/kg was given in the edaravone group; and the same volume of saline was given in the saline group.A model of middle cerebral artery occlusion (MCAO) was induced after 7 days of continuous injection.Cerebral infarct volume was determined by 2,3,5-triphenyltetrazolium staining.Immunohistochemical staining was used to detect TLR4-positive cells in ischemic brain tissue.Reverse transcriptase polymerase chain reaction was used to detect the expression of TLR4/NF-κB mRNA.Results The cerebral infarct volume in mice in the saline,Saussurea involucrata extract and edaravone groups was 131.55± 28.25 mm3,84.10 ±13.92 mm3 and 65.10 ± 6.78 mm3,respectively.There were significant difference (F =10.158,P =0.012).The infarct volume in the Saussurea involucrata extract group (P =0.020) and edaravone group (P0.005) was significantly less than that in the saline group,and there was no significantly difference between the 2 groups.The numbers of cortex and TLR4 positive cells in hippocampus area at the ischemic sides in the saline group were significantly more than those in the sham operation group (all P ＜0.001).The numbers of positive cells of cortex and TLR4 in the Saussurea involucrata extract group and the edaravone group were significantly decreased compared to the saline group (all P ＜ 0.05),and there was no significant differences between the Saussurea involucrata extract group and the edaravone group.The expressions of TLR4,p50,and p65 mRNA in the saline group were significantly up-regulated compared to the sham operation group (all P =0.000).Saussurea involucrata extract could significantly down-regulate the expressions of TLR4,p50,and p65 mRNA at 24 hours after ischemia/reperfusion (all P =0.000).Edaravone could significantly down-regulate the expressions of TLR4 and p65 mRNA (all P =0.000) and it had a down-regulated trend for the expression of p50 mRNA (P =0.053); while there was no significant difference in the expressions of TLR4 and p65 mRNA between the Saussurea involucrata extract group and the edaravone group.Conclusions Saussurea involucrata extract pretreatment may significantly reduce the cerebral infarct volume,down-regulate the expressions of TLR4 and NF-κB subunit,and play a neuroprotective effect by inhibiting inflammatory response after ischemia.
