脊髓损伤后诱导型一氧化氮合酶的表达及药物治疗-外科学专业论文.docxVIP

The The expression of iNOS after experimental删cord mjury and medication treatment To evaluated the effect of Aminoguanidine and Dexamethasone Oll inducible NOS expression and neurological function in a model of spinal cord injury． The spinal cord injur,-y model reported by Nystrom was used to result in moderate cord injury(35．09，10min)．Wistar rats with an average weight of 2309 were randomly divided into following groups：Group A：not injury；Group B：untreated injury；Group C：injury treated with Aminoguanidine；Group D： injury treated with Dexamethasone．At 6，12，24，and 72 hours，after surgery， animals were killed to study the level of iNOS in spinal cord by immunohisto- chemical；At 24，48，72 hours and 1，week，neurological function of hindlimb was assessed by blinded observer using an established multiple test method(mo- tor；toe spread；reflexes to extension，pain；inchned plane and swim test)with tests graded and results expressed as a combined behavioral score． There was a significant difference among groups in iNOS expression．Group C and D was lower than group B(P=0。008，0．007at 24h after surgery)．Be— havioral scores over time showed a significant difference among four Groups． ·2· 1)．The 1)．The expression of iNOS call be inhibited by Aminoguanidine or Dexam- ethasone． 2)。Aminoguanidine and Dexamethasone significantly enhance neurological recovery· Key words：Nitric Oxides，iNOS，Dexamethasone，Aminoguanidine，Spi— nal cord injury ·3· 英文缩略语·4· 英文缩略语 ·4· 前 前 言 脊髓继发性损伤是脊髓损伤的特有反应。关于继发性损伤，一般认为 是脊髓伤后水肿、局部压力增高、微循环障碍以及血管活性物质儿茶酚胺、 多巴胺的升高、自由基介导的脂质过氧化反应和兴奋性氨基酸毒性作用等 综合因素作用。通过研究发现，它们都与iNOS催化生成的NO有关 。 NO是兼有细胞间第二信使和细胞毒性作用的气体性神经活性物质，NO过 量或失调将导致细胞损伤甚至死亡。 近年来，随着对NO研究的深入，其在中枢神经系统中的作用也更加受 到关注，大量研究表明，神经缺血、刨伤、感染和免疫性疾病等引起的神经损 伤可诱导iNOS合成过量NO，具有直接的神经毒性旧o；NOS抑制剂可对抗 这一过程而发挥神经保护作用，提示NOS在神经损伤和修复中起重要作 用∞]。目前，对NOS抑制剂在神经系统中的作用的研究方兴未艾，特别是 在脑缺血、创伤、慢性退行性病变、疼痛等方面研究取得了很大进步。 因为NO同时存在着许多重要的生理功能，如eNOS催化生成的内皮型 NO具有扩张血管、防止血小板聚集和黏附的作用卜o。因此，保留此种NO 重要的生理功能，而抑制iNOS产生的NOS所介导的神经毒性作用应成为 治疗脊髓损伤更行之有效的方法。本实验就是应用特异性的iNOS抑制剂 地塞米松