Aladag M A, Turkoz Y, Sahna E, Parlakpinar H, Gul M
Department of Neurosurgery, Medical School of Inonu University, Turgut Ozal Medical Center, 44069 Malatya, Turkey.
Acta Neurochir (Wien). 2003 Aug;145(8):673-7. doi: 10.1007/s00701-003-0052-z.
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.
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 (37 degrees C) 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 sacrificed 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.
Administration of MnTBAP significantly attenuated the vasoconstriction of the basilar artery in group 4 compared with the groups 2 and 3 (p<0.001).
These results suggest that this SOD mimetic (MnTBAP) attenuates delayed cerebral vasoconstriction following experimental SAH and that superoxide anions have a role in the pathogenesis of vasospasm after SAH.
迟发性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）的过表达可减轻脑血管痉挛的程度。因此，我们研究了一种新型、稳定且可透过细胞膜的超氧化物歧化酶模拟物MnTBAP [Mn(III)四（4-苯甲酸）卟啉]能否预防血管痉挛，该模拟物可穿透生物膜并清除超氧阴离子和过氧亚硝酸盐。
将28只大鼠（225 - 250克）平均分为四组：第1组：对照组；第2组：仅蛛网膜下腔出血（SAH）组；第3组：SAH加安慰剂组；第4组：SAH加MnTBAP组。我们采用双次出血法制造SAH。SAH后6小时开始，分别对第4组和第3组大鼠每日腹腔注射两次5毫克/千克的MnTBAP（德国达姆施塔特卡尔生物化学公司；产品编号475870）或等体积的0.9%生理盐水（37摄氏度），持续5天。SAH后直至第5天持续注射MnTBAP或0.9%生理盐水，第5天处死大鼠。通过光学显微镜检查脑桥水平的脑切片。用测微计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。
与第2组和第3组相比，第4组给予MnTBAP后基底动脉的血管收缩明显减轻（p<0.001）。
这些结果表明，这种超氧化物歧化酶模拟物（MnTBAP）可减轻实验性SAH后的迟发性脑血管收缩，并提示超氧阴离子在SAH后血管痉挛的发病机制中起作用。
