Lee H Y, Lee J S, Kim E J, Han J W, Lee H W, Kang Y J, Chang K C
Department of Pharmacology, College of Medicine, Konyang University, Nonsan, Korea.
Arch Pharm Res. 1999 Feb;22(1):55-9. doi: 10.1007/BF02976436.
Nitric oxide synthesized by inducible nitric oxide synthase (iNOS) has been implicated as a mediator of inflammation in rheumatic and autoimmune diseases. The effects of higenamine, a tetrahydroisoquinoline compound, on induction of NOS by bacterial lipopolysaccharide (LPS) were examined in murine peritoneal macrophages. LPS-induced nitrite/nitrate production was markedly inhibited by higenamine which at 0.01 mM, decreased nitrite/nitrate levels by 48.7+/-4.4%. This was comparable to the inhibition of LPS-induced nitrite/nitrate production by tetrandrin (49.51+/-2.02%) at the same concentration. Northern and Western blot analysis of iNOS expression demonstrated that iNOS expression was significantly attenuated following co-incubation of peritoneal macrophages with LPS (10 microg/ml; 18 hrs) and higenamine (0.001, 0.01 mM; 18 hrs). These results suggest that higenamine can inhibit LPS-induced expression of iNOS mRNA in murine peritoneal macrophages. The clinical implications of these findings remain to be established.
诱导型一氧化氮合酶（iNOS）合成的一氧化氮被认为是风湿性和自身免疫性疾病炎症的介质。在小鼠腹腔巨噬细胞中研究了四氢异喹啉化合物去甲乌药碱对细菌脂多糖（LPS）诱导一氧化氮合酶（NOS）的影响。去甲乌药碱显著抑制LPS诱导的亚硝酸盐/硝酸盐生成，在0.01 mM时，亚硝酸盐/硝酸盐水平降低48.7±4.4%。这与相同浓度的粉防己碱（49.51±2.02%）对LPS诱导的亚硝酸盐/硝酸盐生成的抑制作用相当。对iNOS表达的Northern和Western印迹分析表明，将腹腔巨噬细胞与LPS（10μg/ml；18小时）和去甲乌药碱（0.001、0.01 mM；18小时）共同孵育后，iNOS表达显著减弱。这些结果表明，去甲乌药碱可抑制小鼠腹腔巨噬细胞中LPS诱导的iNOS mRNA表达。这些发现的临床意义尚待确定。
