一氧化氮参与脑缺血耐受过程中Ⅱ组代谢型谷氨酸受体的作用

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目的:探讨一氧化氮在Ⅱ组代谢型谷氨酸受体(metabotropicglutamatereceptors,mGluRs)参与海马脑缺血预处理cerebralischemicprecondi-(tioning,CIP)保护机制中的作用,从整体水平探讨mGluRs对一氧化氮参与脑缺血耐受的影响。方法:实验于2003-03/04在河北医科大学病理生理学研究室进行。51只永久凝闭椎动脉的SD大鼠随机分为假手术组、CIP组、MTPG+CIP组、损伤性缺血组、MTPG+CIP+损伤性缺血组5组。后4组大鼠均在末次缺血再灌后即刻,6,24,72h取材,观察脑室应用Ⅱ组mGluRs阻断剂α-甲基-(4-四唑基-苯)甘氨酸(MTPG)对CIP后一氧化氮合酶(nitricoxidesynthase,NOS)活性和一氧化氮生成的影响。结果:NOS的活性于3min的CIP后再灌注6h时开始升高,为(155.0±33.5)nkat/g,24h达高峰,为(202.0±37.2)nkat/g,72h降至假手术组水平,为(123.8±27.5)nkat/g。应用MTPG后可见,NOS的活性受到明显抑制,较单纯CIP组明显减低(P<0.05);NOS的活性于8min的全脑缺血后再灌注6h开始升高,24h达高峰,72h降至起始水平,明显高于CIP组相应时点。MTPG+CIP+损伤性缺血组中NOS的活性较MTPG+CIP组明显升高,与单纯8min的损伤性缺血组比较无明显差别。结论:MTPG能阻断CIP引起的NOS的表达增加,同时又能阻断CIP抗后续损伤性缺血的作用,提示一氧化氮 AIM: To investigate the role of nitric oxide in metablism glutamate receptors (mGluRs) in the protective mechanism of hippocampus cerebral ischemic preconditioning (CIP), and to explore the effect of mGluRs on nitric oxide Participation in cerebral ischemic tolerance. Methods: The experiment was performed in the Pathophysiology Laboratory of Hebei Medical University from March to April in 2003. Fifty-one SD rats with permanent vertebral artery occlusion were randomly divided into 5 groups: sham operation group, CIP group, MTPG + CIP group, ischemic injury group and MTPG + CIP + ischemic injury group. The rats in the latter 4 groups were taken immediately after the last ischemia / reperfusion, and the ventricular application of mGluRs blocker α-methyl- (4-tetrazolyl-benzene) glycine (MTPG) Effect of nitric oxide synthase (NOS) activity and nitric oxide production after CIP. Results: The activity of NOS began to rise at 6h after 3min reperfusion, reached the peak at (155.0 ± 33.5) nkat / g at 24h, reached the peak at (202.0 ± 37.2) nkat / g at 24h and decreased to the level of sham operation group at 72h (123.8 ± 27.5) nkat / g. After MTPG application, the activity of NOS was significantly inhibited (P <0.05). The activity of NOS began to increase at 6h after reperfusion at 8min, peaked at 24h and dropped to the level of 72h The initial level was significantly higher than that of CIP group. Compared with MTPG + CIP group, the activity of NOS in MTPG + CIP + ischemic insult group was significantly higher than that in MTPG + CIP + ischemic insult group. CONCLUSION: MTPG can block the increase of NOS induced by CIP and at the same time block the effect of CIP on the subsequent injury of ischemia, suggesting that nitric oxide
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