Moochhala Shabbir M, Lu Jia, Xing Michelle Chang Ker, Anuar Farhana, Ng Kian Chye, Yang Kerwin Low Siew, Whiteman Matthew, Atan Shirhan
Defence Medical and Environmental Research Institute@DSO, Singapore.
J Trauma. 2005 Aug;59(2):450-7. doi: 10.1097/01.ta.0000174858.79847.6d.
The present study examined the temporal expression of nitric oxide synthase (iNOS) and cyclo-oxygenase (COX)-2 in rat brains after traumatic brain injury (TBI). We studied the effects of mercaptoethylguanidine (MEG), a dual inhibitor of the inducible iNOS and COX with scavenging effect on peroxynitrite, on physiologic variables, brain pathogenesis, and neurologic performance in rats after a lateral fluid percussive-induced TBI. Mean arterial blood pressure and percentage cerebral tissue perfusion in MEG-treated TBI rats showed significant improvement when compared with TBI rats. Immunohistochemical analysis showed a marked number of iNOS and COX-2 immunopositive cells in the cerebral cortex ipsilateral to the injury in TBI rats when compared with MEG-treated TBI rats. MEG also significantly decreased the number of hyperchromatic and shrunken cortical neurons when compared with TBI rats' brain nitrate/nitrite, and prostaglandin E2 levels were attenuated in MEG-treated TBI rats when compared with TBI rats. It is therefore suggested that treatment of MEG via inhibition of iNOS and COX-2 might contribute to improved physiologic variables, neuronal cell survival, and neurologic outcome after TBI.
本研究检测了创伤性脑损伤（TBI）后大鼠脑内一氧化氮合酶（iNOS）和环氧化酶（COX）-2的时序表达。我们研究了巯基乙胍（MEG），一种对过氧亚硝酸盐具有清除作用的诱导型iNOS和COX双重抑制剂，对侧方流体冲击诱导的TBI大鼠生理变量、脑病理变化及神经功能表现的影响。与TBI大鼠相比，MEG治疗的TBI大鼠平均动脉血压和脑组织灌注百分比有显著改善。免疫组化分析显示，与MEG治疗的TBI大鼠相比，TBI大鼠损伤同侧大脑皮质中iNOS和COX-2免疫阳性细胞数量明显增多。与TBI大鼠相比，MEG还显著减少了大脑皮质中深染和皱缩神经元的数量，并且与TBI大鼠相比，MEG治疗的TBI大鼠脑内硝酸盐/亚硝酸盐和前列腺素E2水平降低。因此，提示通过抑制iNOS和COX-2进行MEG治疗可能有助于改善TBI后的生理变量、神经元细胞存活及神经功能转归。
