Nitric Oxide Scavenger Carboxy-PTIO Reduces Infarct Volume Following Permanent Focal Ischemia

一氧化氮補捉物Carboxy-PTIO降低永久性腦梗塞的神經保護作用－初步報告

方詩元(Shih-Yuan Fang) ； 曾稼志(Chia-Chih Tseng) ； 楊曜臨(Yao-Lin Yang) ； 李宜堅(E-Jian Lee) ； 陳鴻儀(Hung-Yi Chen) ； Anish Bhardwaj ； 陳宗鷹(Tsung-Ying Chen)

《Acta Anaesthesiologica Taiwanica》 44卷3期 (2006/09) Pp. 141-146

摘要

背景：一氧化氮(NO)被報告於大腦缺血時扮演著神經保護與神經毒性的雙重角色。自由離子補捉物則在大腦缺血時據有保護大腦組織的功能。因此我們檢測一氧化氮補捉物2-(4-carboxyphenyl)-4，4，5，5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO)在大鼠與小鼠永久性中大腦動脈阻塞時的神經保護作用。
方法：我們使用中大腦動脈(middle cerebral artery， MCA)永久性梗塞的動物模式。在誘發中大腦動脈阻塞前一個小時，31隻Sprague-Dawley大鼠分別在腹腔內注射carboxy-PTIO (0.3， 0.6mg/kg)或生理食鹽水。另一個實驗，則使用49隻C57BL/6NCrj小鼠進行誘發中大腦動脈阻塞之後30分鐘，於腹腔注射carboxyl-PTIO (0.6， 1.2mg/kg)或生理食鹽水。於22-24小時之後，評估神經行為分數，及用2，3，5-triphenyltetrazolium (TTC)腦部染色切片定量影像分析梗塞範圍。
結果：實驗結果顯示事先於大鼠發生中大腦動脈阻塞前一小時給予0.6 mg/kg carboxy-PTIO腹腔內注射，有效的降低梗塞面積的範圍（實驗組19.9±2.9%；n=10 vs.控制組29.2±2.7%；n=16），但在0.3mg/kg劑量則無差異(28.3±8.4%; n=5)。另一小鼠實驗於發生中大腦動脈阻塞後30分鐘給予0.6 mg/kg carboxy-PTIO (30.3±3.9%; n=16)，亦有效降低梗塞面積的範圍（控制組：46.1±2.8%；n=18）。
結論：初步的研究結論為在中大腦動脈永久性梗塞造成的局部大腦缺血，不管事先於大鼠或事後於小鼠模式給予0.6 mg/kg carboxy-PTIO皆可提供神經保護作用。

關鍵字

腦缺血 ； 一氧化氮 ； 自由基清除者 ； 神經保護劑

並列摘要

Background: Nitric oxide (NO) has been shown to play a dual role as a neuroprotectant and a neurotoxin in cerebral ischemia. Free radical scavengers protect brain tissue from ischemic injury. Consequently, we examined the neuroprotective action of NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), in cerebral ischemia induced by permanent middle cerebral artery occlusion (MCAO) in rats and mice.
Methods: All experiments were performed in a randomized fashion. In the first series of experiments, adult Sprague-Dawley rats (n=31) subjected to permanent MCAO were treated with carboxy-PTIO (0.3, 0.6 mg/kg) or vehicle (normal saline) injected intraperitoneally (IP) 1 hr before permanent MCAO. In the second series of experiments, adult C57BL/6NCrj mice (n=49) were treated with carboxy-PTIO (0.6, 1.2 mg/kg) or vehicle saline 30 min following MCAO. Neurobehavioral scores were determined 22-24 hr following permanent MCAO and infarct volumes determined by quantitative image analysis of 2,3,5-triphenyltetrazolium (TTC)-stained brain sections.
Results: Pre-treatment with carboxy-PTIO at 0.6 mg/kg IP in rats significantly attenuated infarct volume (19.9±2.9%; n=10) as compared with vehicle-treated controls (29.2±2.7%; n=16), but not at 0.3 mg/kg (28.3±8.4%; n=5). Post-MCAO treatment in mice with 0.6 mg/kg carboxy-PTIO (30.3±3.9%; n=16) significantly attenuated infarct volume as compared with vehicle-treated controls (46.1±2.8%; n=18).
Conclusions: These data demonstrate that NO scavenger, carboxy-PTIO, provides significant ischemic neuroprotection when given as a pre-treatment as well as after the onset of permanent focal ischemia in two animal species.

並列關鍵字

Brain ischemia ； Nitric oxide ； Free radical scavengers ； Neuroprotective agents