Kasama T, Kobayashi K, Sekine F, Negishi M, Ide H, Takahashi T, Niwa Y
Department of Internal Medicine, School of Medicine, Showa University, Japan.
Life Sci. 1988;43(23):1887-96. doi: 10.1016/s0024-3205(88)80006-7.
Because reactive oxygen species (ROS) are generally believed to play an important role in tissue injury in rheumatoid arthritis, we examined the levels of lipid peroxides, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in the synovial membrane, serum and liver of young (8 wk) and old (12 mo) mice with collagen-induced arthritis. In the synovial membrane, serum and liver, lipid peroxide levels of both young and old mice were increased beginning on the 3rd day after the onset of arthritis. SOD activity, which scavenges O2- and inhibits lipid peroxidation, rose markedly in the synovial membrane of young mice in parallel with the increase in lipid peroxide levels, but not so markedly in old mice. Liver GSH-Px activity, which metabolizes already formed lipid peroxides, also rose in young arthritic mice to a greater degree than in old mice. This study suggests that in inflammatory synovial lesions, lipid peroxides are generated due to an increase in ROS concentration, with resultant cytotoxicity, and that younger animals or humans can prevent this unfavorable reaction more effectively than aged ones by enzyme induction. The hypothesis that lipid peroxides formed in the oxidative lesions of the primary organ are released into the serum, trapped by the liver and metabolized there is further supported by the present study.
由于一般认为活性氧（ROS）在类风湿性关节炎的组织损伤中起重要作用，我们检测了胶原诱导性关节炎的年轻（8周龄）和老年（12月龄）小鼠滑膜、血清和肝脏中脂质过氧化物、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）的水平。在滑膜、血清和肝脏中，年轻和老年小鼠的脂质过氧化物水平在关节炎发病后第3天开始升高。清除O2-并抑制脂质过氧化的SOD活性在年轻小鼠的滑膜中随着脂质过氧化物水平的升高而显著升高，但在老年小鼠中升高不明显。代谢已形成的脂质过氧化物的肝脏GSH-Px活性在年轻关节炎小鼠中也比老年小鼠升高程度更大。本研究表明，在炎性滑膜病变中，由于ROS浓度升高产生脂质过氧化物，导致细胞毒性，并且年轻动物或人类比老年动物或人类能通过酶诱导更有效地预防这种不利反应。原发性器官氧化损伤中形成的脂质过氧化物释放到血清中，被肝脏捕获并在肝脏中代谢的假说得到了本研究的进一步支持。
