Reactive oxygen species induced apoptosis in ischemia-reperfusion injury

用电子顺磁共振(EPR)和流式细胞术研究了6-甲酰蝶呤(6FP)、香叶基香叶内酮(GGA)和异丙酚对缺血再灌注损伤和活性氧(ROS)产生的影响。1)观察了6FP对硝基酪氨酸(作为酪氨酸硝化足迹)生成的影响。结果表明，6FP不一定是过氧化氢的强清除剂。2)观察了6FP对巨噬细胞产生一氧化氮(NO)的影响。结果表明，6FP同时抑制iNOS诱导和NOS活性，从而抑制NO的产生。3)检测GGA对乙醇诱导的大鼠肝细胞毒性的影响。结果表明，GGA促进了抗氧化剂硫氧还蛋白的诱导，对肝细胞具有保护作用。4)对6FP的化学性质及其生物学功能进行了检测。结果表明，6FP与NAD(P)H等还原剂反应产生ROS，诱导细胞凋亡，抑制细胞增殖，抑制Fas诱导的细胞凋亡。5)观察异丙酚对局灶性脑缺血大鼠神经元损伤的影响。结果表明，异丙酚可抑制脑内乳酸蓄积和脑水肿的形成，从而减轻神经元损伤。

Effects of 6-formylpterin (6FP), geranylgeranylacetone (GGA) and propofol on the production of reactive oxygen species (ROS) and ischemia-reperfusion injury were investigated using electron paramagnetic resonance (EPR) and flow cytometry.1) Effects of 6FP on the production of nitrotyrosine as a footprint of tyrosine nitration by peroxynitite, a strong oxidant, were examined. The results showed that 6FP was not necessarily a strong scavenger of peroxynitite.2) Effects of 6FP on the production of nitric oxide (NO) in macrophages were examined. The results showed that 6FP suppressed both iNOS induction and NOS activity, which resulted in the inhibition of NO production.3) Effects of GGA on ethanol-induced cytotoxicity in rat hepatocytes were examined. The results showed that GGA facilitated the induction of thioredoxin, an antioxidant, which exerted the cytoprotective effects on the hepatocytes.4) The chemical property of 6FP and its biological functions were examined. The results showed that 6FP reacted with reducing agents, such as NAD(P)H, and generated ROS, which induced apoptosis, suppression of cell proliferation and inhibition of Fas-induced apoptosis.5) Effects of propofol on neuronal damage in focal cerebral ischemia in hyperglycemic rats were examined. The results showed that ppropofol suppressed lactate accumulation and edema formation in brain, which resulted in the attenuation of the neuronal damage.