The attenuation of vasospasm by using a SOD mimetic after experimental subarachnoidal haemorrhage in rats

The attenuation of vasospasm by using a SOD mimetic after experimental subarachnoidal haemorrhage in rats
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DOI:
10.1007/s00701-003-0052-z
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发表时间:
2003-08-01
影响因子:
2.4
通讯作者:
Gul, M
Gul, M
中科院分区:
医学3区
文献类型:
--
作者:
Aladag, MA;Turkoz, Y;Gul, M

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背景。延迟脑血管收缩和脑缺血是颅内动脉瘤破裂患者治疗中的关键问题。铜锌超氧化物歧化酶(Cu-Zn SOD)的过度表达可以减轻脑血管痉挛的程度。因此,我们研究了是否可以通过一种新型、稳定且可渗透细胞的 SOD 模拟物 MnTBAP [Mn(III) 四(4-苯甲酸)卟啉] 来预防血管痉挛,该模拟物可渗透生物膜并清除超氧阴离子和过氧亚硝酸盐。方法。 28只大鼠(225-250g)平均分为四组:第1组:对照组;第 2 组:仅 SAH;第3组:SAH加安慰剂;第4组:SAH加MnTBAP 我们使用双出血法来产生SAH。 SAH后6小时开始,第4组和第3组分别通过腹腔注射每天两次,连续5天施用5mg/kg MnTBAP(Calbiochem,达姆施塔特-德国;货号475870))或等体积的0.9%盐水(37℃)。 MnTBAP或0.9%盐水注射持续至SAH后第五天,并在第五天处死大鼠。通过光学显微镜检查脑桥水平的脑切片。用千分尺对基底动脉管腔和血管壁(内膜加中膜)的横截面积进行平面测量。发现。与第 2 组和第 3 组相比,施用 MnTBAP 显着减弱第 4 组基底动脉的血管收缩(p
Background. Delayed cerebral vasoconstriction and brain ischemia, are critical problems in the management of a patient affected by rupture of an intracranial aneurysm. Overexpression of Cu-Zn superoxide dismutase (Cu-Zn SOD) can reduce the extent of cerebral vasospasm. We, therefore investigated if vasospasm, can be prevented by a novel, stable, and cell permeable SOD mimetic, MnTBAP [Mn(III) tetrakis (4-benzoic acid) porphyrin] which permeates the biological membranes and scavenges superoxide anions and peroxynitrite.Methods. 28 rats (225-250 g) were divided equally into four groups: group 1: control; group 2: SAH only; group 3: SAH plus placebo; and group 4: SAH plus MnTBAP We used a double haemorrhage method to produce SAH. Starting six hours after SAH, 5 mg/kg MnTBAP (Calbiochem, Darmstadt-Germany; Cat. No 475870)) or an equal volume of 0.9% saline (37degreesC) was administered by intraperitoneal injection twice daily for 5 days to groups 4 and 3 respectively. MnTBAP or 0.9% saline injections were continued up to fifth day after SAH and rats were sacrificied on the fifth day. Brain sections at the level of the pons were examined by light microscopy. Planimetric measurements were made for the cross-sectional areas of the lumen and the vessel wall (intima plus media) of the basilar artery by a micrometer.Finding. Administration of MnTBAP significantly attenuated the vasoconstriction of the basilar artery in group 4 compared with the groups 2 and 3 (p