中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2007年
6期
455-461
,共7页
孙晓彩%羡晓辉%蔡劲松%李文斌%张敏%李清君
孫曉綵%羨曉輝%蔡勁鬆%李文斌%張敏%李清君
손효채%이효휘%채경송%리문빈%장민%리청군
有丝分裂素激活蛋白激酶类%SB 203580%缺血预适应%脑缺血%超氧化物岐化酶%丙二醛
有絲分裂素激活蛋白激酶類%SB 203580%缺血預適應%腦缺血%超氧化物岐化酶%丙二醛
유사분렬소격활단백격매류%SB 203580%결혈예괄응%뇌결혈%초양화물기화매%병이철
mitogen-activated protein kinases%SB 203580%ischemic preconditioning%brain ischemia%superoxide dismutase%malondialdehyde
目的 探讨超氧化物岐化酶(SOD)在p38有丝分裂素激活蛋白激酶(MAPK)介导的肢体缺血预适应(LIP)脑保护中的作用.方法 永久凝闭椎动脉的Wistar大鼠,重复夹闭双侧股动脉3次(每次10 min,间隔10 min)作为LIP,之后即刻夹闭双侧颈总动脉8 min造成全脑缺血.SB 203580+LIP+脑缺血组于LIP前30 min侧脑室内注射p38 MAPK抑制剂SB 203580 (100 μmol·L-1, 25 μL).黄嘌呤氧化酶法测定海马SOD活性,硫代巴比妥酸法测定海马丙二醛(MDA)含量,硫堇染色观察海马的组织学分级.结果 LIP显著抑制脑缺血引起的海马CA1区SOD活性下降、MDA含量增加及延迟性神经元死亡.预先侧脑室注射SB 203580显著阻断LIP对缺血脑组织的上述保护作用.结论 SOD可能作为p38 MAPK的下游分子参与LIP诱导的脑缺血耐受.
目的 探討超氧化物岐化酶(SOD)在p38有絲分裂素激活蛋白激酶(MAPK)介導的肢體缺血預適應(LIP)腦保護中的作用.方法 永久凝閉椎動脈的Wistar大鼠,重複夾閉雙側股動脈3次(每次10 min,間隔10 min)作為LIP,之後即刻夾閉雙側頸總動脈8 min造成全腦缺血.SB 203580+LIP+腦缺血組于LIP前30 min側腦室內註射p38 MAPK抑製劑SB 203580 (100 μmol·L-1, 25 μL).黃嘌呤氧化酶法測定海馬SOD活性,硫代巴比妥痠法測定海馬丙二醛(MDA)含量,硫堇染色觀察海馬的組織學分級.結果 LIP顯著抑製腦缺血引起的海馬CA1區SOD活性下降、MDA含量增加及延遲性神經元死亡.預先側腦室註射SB 203580顯著阻斷LIP對缺血腦組織的上述保護作用.結論 SOD可能作為p38 MAPK的下遊分子參與LIP誘導的腦缺血耐受.
목적 탐토초양화물기화매(SOD)재p38유사분렬소격활단백격매(MAPK)개도적지체결혈예괄응(LIP)뇌보호중적작용.방법 영구응폐추동맥적Wistar대서,중복협폐쌍측고동맥3차(매차10 min,간격10 min)작위LIP,지후즉각협폐쌍측경총동맥8 min조성전뇌결혈.SB 203580+LIP+뇌결혈조우LIP전30 min측뇌실내주사p38 MAPK억제제SB 203580 (100 μmol·L-1, 25 μL).황표령양화매법측정해마SOD활성,류대파비타산법측정해마병이철(MDA)함량,류근염색관찰해마적조직학분급.결과 LIP현저억제뇌결혈인기적해마CA1구SOD활성하강、MDA함량증가급연지성신경원사망.예선측뇌실주사SB 203580현저조단LIP대결혈뇌조직적상술보호작용.결론 SOD가능작위p38 MAPK적하유분자삼여LIP유도적뇌결혈내수.
AIM To explore the role of superoxide dismutase (SOD) in the p38 mitogen-activated protein kinase (MAPK) mediated brain ischemic tolerance induced by limb ischemic preconditioning (LIP). METHODS The Wistar rats with permanent occlusion of the bilateral vertebral arteries were subjected to occlude the bilateral femoral arteries for 10 min, 3 times, at an interval of 10 min to get the LIP, then global brain ischemia was induced immediately by occluding the bilateral common carotid arteries for 8 min. SB 203580 (100 μmol·L-1, in a volume of 25 μL), an inhibitor of p38 MAPK, was intraventricularly injected 30 min before LIP in SB 203580+LIP+brain ischemia group. Xanthinoxidase and thiomalonylurea methods were used to determine SOD activity and malondialdehyde (MDA) content of the hippocampus, respectively. Thionin staining was used for observing histological changes of the hippocampus. RESULTS LIP significantly prevented the decrease of SOD activity, the increase of MDA content and the delayed neuronal death in the CA1 hippocampus induced by the brain ischemia. SB 203580 pretreatment evidently blocked the protective effect of LIP against the delayed neuronal death and the modulation on SOD activity and MDA content. CONCLUSIONSOD may play an important role served as a downstream molecule of p38 MAPK in the induction of brain ischemic tolerance by LIP.
