Orihara Y
Department of Legal Medicine, Nagasaki University School of Medicine.
Nihon Hoigaku Zasshi. 2000 Nov;54(3):361-6.
Inducible nitric oxide synthase (iNOS) does not express within cells under normal conditions. But, it is induced by inflammatory cytokines and the activity of iNOS is independent of elevated Ca2+. It is implied that nitric oxide (NO) produced by iNOS has a close relation with pathological conditions as a mediator of cell damages. We aimed at the crucial property of iNOS, therefore we have searched the expression of iNOS for the purpose to establish forensic pathological significance in the cases with damages of neuronal cells or cardiomyocytes. At first, we examined induction and expression of iNOS in the human brains whose causes of death was traumatic brain injury (TBI). These findings demonstrated prolonged induction of iNOS in neutrophils, microglia/macrophages, and vascular smooth muscle cells in traumatized brain. Such a response may indicate that iNOS could play a crucial role on cerebrovascular disturbances and secondary brain injury subsequent to TBI. Secondly, we evaluated the induction and expression of iNOS in the human hearts with myocardial cell damage. The expressions of iNOS were localized to the following areas, the cardiomyocytes in the zone adjacent to the infarcted area, the preserved cytoplasm of infarcted cardiomyocytes, the endothelial cells in arteriolar walls and macrophages in viable myocardium. These findings have led to the speculation that the NO might play a significant role during myocardial ischemia and reperfusion. Furthermore, representative expression of iNOS was identified in coronary artery, that is the portion of shoulder and broken part of coronary atherosclerotic plaque. These findings may indicate that the iNOS might have a close relation to the coronary atherosclerotic lesion. The physiopathological mechanism of iNOS might involve in the close relation with inflammatory cytokines. The precise elucidation of this participation may make it possible to explicate the presumed time of injury in an earlier stage, and to clarify the forensic pathological significance of these inflammatory factors.
诱导型一氧化氮合酶（iNOS）在正常条件下细胞内不表达。但是，它可被炎性细胞因子诱导，且iNOS的活性不依赖于细胞内钙离子浓度升高。这意味着iNOS产生的一氧化氮（NO）作为细胞损伤的介质，与病理状况密切相关。因此，我们针对iNOS的关键特性，为了确定其在神经元细胞或心肌细胞损伤案件中的法医病理学意义，研究了iNOS的表达情况。首先，我们检测了因创伤性脑损伤（TBI）致死的人类大脑中iNOS的诱导和表达情况。这些研究结果表明，在创伤性脑损伤后的大脑中，中性粒细胞、小胶质细胞/巨噬细胞以及血管平滑肌细胞中iNOS的诱导时间延长。这种反应可能表明iNOS在TBI后的脑血管紊乱和继发性脑损伤中起关键作用。其次，我们评估了心肌细胞损伤的人类心脏中iNOS的诱导和表达情况。iNOS的表达定位于以下区域：梗死区域相邻地带的心肌细胞、梗死心肌细胞残留的细胞质、小动脉壁内皮细胞以及存活心肌中的巨噬细胞。这些研究结果促使人们推测，NO可能在心肌缺血和再灌注过程中发挥重要作用。此外，在冠状动脉中发现了iNOS的典型表达，即在冠状动脉粥样硬化斑块的肩部和破裂部位。这些研究结果可能表明iNOS与冠状动脉粥样硬化病变密切相关。iNOS的生理病理机制可能与炎性细胞因子密切相关。对这种参与机制的精确阐释，可能有助于更早地推断损伤发生时间，并阐明这些炎性因子的法医病理学意义。
