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[摘要]
目的 采用体内外炎症模型研究丹参酮ⅡA抗炎活性作用及其作用机制。方法 建立脂多糖(LPS)诱导巨噬细胞RAW264.7细胞体外炎症模型,检测不同浓度丹参酮ⅡA对炎症因子水平、诱导型一氧化氮合酶(iNOS)、环氧化酶2(COX-2)蛋白表达及其基因表达的影响。建立二甲苯致小鼠耳廓肿胀和角叉菜胶大鼠足跖肿胀炎症模型,探讨不同浓度丹参酮ⅡA的体内抗炎作用。结果 丹参酮ⅡA对RAW264.7细胞无明显毒性。与LPS组比较,丹参酮ⅡA剂量在2.5~40 mg/L呈明显剂量相关性地抑制一氧化氮(NO)、白细胞介素-1b(IL-1b)和白细胞介素-6(IL-6)释放(P<0.05、0.01)。与LPS组比较,丹参酮ⅡA呈现剂量相关性地抑制LPS诱导的RAW264.7细胞iNOS和COX-2蛋白的表达(P<0.01)。与LPS组比较,丹参酮ⅡA呈剂量相关性地下调LPS诱导的RAW264.7细胞中的iNOS、COX-2、IL-1b和IL-6基因表达(P<0.05、0.01)。丹参酮ⅡA在10~60 mg/kg对二甲苯所致小鼠耳廓肿胀有不同程度的抑制作用,对角叉菜胶所致大鼠足跖肿胀有不同程度的抑制作用,并呈剂量相关性(P<0.05、0.01),且当丹参酮ⅡA给药剂量达到40 mg/kg时,其抗炎效果强于阿司匹林。结论 丹参酮ⅡA具有抗炎作用,其作用机制可能与减少巨噬细胞炎症介质生成和释放、炎症基因iNOS、COX-2、IL-1b和IL-6的表达密切相关。
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[Abstract]
Objective To study the anti-inflammatory effect and its mechanism of tanshinone ⅡA by inflammation model in vivo and in vitro. Methods An inflammatory model in vitro of macrophages RAW264.7 induced by LPS was established to detect the effects of tanshinone ⅡA with different concentrations on the inflammatory cytokines levels, the expression of iNOS and COX-2 proteins, and the gene expressions. The models of xylene-induced mice ear edema and carrageenan-induced paw edema were established to investigate the anti-inflammatory effects of different concentrations of tanshinone ⅡA in vivo. Results There was no cytotoxicity of tanshinone ⅡA on RAW264.7 cells. Compared with LPS group, tanshinone ⅡA could significantly inhibit the NO, IL-1b, and IL-6 in a dose-dependent manner at 2.5-40 mg/L (P<0.05, 0.01). Compared with LPS group, tanshinone ⅡA could inhibit the expression of iNOS and COX-2 protein in RAW264.7 cells induced by LPS in a dose-dependent manner (P<0.01). Compared with LPS group, tanshinone ⅡA could down-regulate the levels of iNOS, COX-2, IL-1b and IL-6 genes in RAW264.7 cells induced by LPS in a dose-dependent manner (P<0.05, 0.01). Tanshinone ⅡA (10-60 mg/kg) could show different degree of inhibitory effect on ear edema of mice caused by xylene and paw edema of rats caused by carrageenan with a dose correlation (P<0.05, 0.01). When the dose of tanshinone ⅡA reached 40 mg/kg, its anti-inflammatory effect was stronger than aspirin. Conclusion Tanshinone ⅡA has a direct anti-inflammatory effect, which is related to macrophage inflammatory mediator production and release and the genes expression of iNOS, COX-2, IL-1b and IL-6.
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