目的:研究重组人超氧化物歧化酶(rhSOD)的抗炎作用及其作用机理.方法:采用角叉菜胶诱导的大鼠和小鼠关节炎、巴豆油诱发的小鼠耳肿模型,研究药物对炎症肿胀度的影响.大鼠炎症渗出液中NOS活性用NADPH黄递酶染色法、β-NAG用对硝基酚比色法、MDA用TBA荧光法测定,IL-1β和TNFo含量用放射免疫法测定.结果:rhSOD 20-80mg/kg ip对大鼠关节炎,40-80mg/kg im对小鼠耳肿、80mg/kg ip对小鼠足肿有显著的抑制作用同时大鼠炎症渗出液中NOS活性降低,IL-lβ和TNFα含量显著减少.其抑制IL-1β生成的作用明显强于地塞米松2 mg/kg ip.rhSOD使炎症组织内中性粒细胞浸润减轻、MDA生成减少,但不影响炎症渗出液中β-NAG活性.结论:rhSOD对大鼠和小鼠实验性炎症有明显的抗炎作用.其抗炎作用机理和清除氧自由基、抗脂质过氧化有关,也和抑制炎症细胞浸润、减少炎症性细胞因子如IL-1β和TNFα的生成有关.%AIM: To investigate the anti-inflammatory effects and mechanism of recombinant human superoxide dismutase (rhSOD). METHODS: Inflammation models such as croton oil-induced ear swelling and carrageenan-induced hind paw edema in mice and rats were prepared. The nitric oxide synthase (NOS) activity was measured by NADPH-diaphoras stain assay, N-acetyl-β-D-glucosaminidase (β-NAG) activity by spectrophotography, malondialdehyde (MDA) content by thiobarbituric acid (TBA)fluorescence technique, and interleukin-1β (IL-Iβ),tumor necrosis factor α (TNFα), and IL-8 content by radioimmunoassay (RIA). RESULTS: rhSOD 20-80mg/kg ip, 40- 80 mg/kg im, and 80 mg/kg ip significantly inhibited carrageenan-induced paw edema in rats, croton oil-induced ear swelling in mice, and carrageenan-induced hind paw edema in mice, respectively. In the rat arthritis induced by carrageenan,rhSOD 40 mg/kg reduced MDA content in inflamed paws, inhibited NOS activity, and lowered the content of IL-1β and TNFα in exudate significantly. The inhibitory effect of rhSOD 40 mg/kg ip on IL-1β production was more evident than that of dexamethasone 2 rog/kg ip.Also rhSOD obviously inhibited neutrophil infiltration;However, rhSOD had no effect on β-NAG activity in exudate. CONCLUSION: rhSOD has anti-inflammatory effect on experimental inflammation in rats and mice, and its mechanisms are relevant to oxygen free radical scavenging, anti-lipid peroxidation, inhibition of neutrophil infiltration, and formation of inflammatory cytokines.
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