Roch-Arveiller M, Maman L, Huy D P, Fontagne J, Giroud J P, Sorenson J R
Department of Pharmacology-CNRS URA 595, Hôpital Cochin, Paris, France.
Inflamm Res. 1995 May;44(5):198-203. doi: 10.1007/BF01782258.
Antiinflammatory activities and modulations of PMNL responses produced by treatment with tetrakis-mu-2-[3-(trifluoromethyl)-phenyl]aminonicotinatodicopper (II) [Cu(II)2(niflumate)4] and niflumic acid were studied in isologous serum-induced rat pleurisy. Doses of 10 or 30 mg/kg (35 or 106 mumol/kg) of niflumic acid or Cu(II)2(niflumate)4 (8 or 23 mumol/kg) caused significant (p < 0.01) reductions in pleural exudate and number of polymorphonuclear leukocytes (PMNLs) in the exudate. While both doses of Cu(II)2(niflumate)4 produced significant dose-related reductions in both parameters, only the higher dose of niflumic acid produced a significant dose-related reduction in both parameters. Boyden chamber measurements of N-formyl-methionyl-leucyl-phenylalanine (f-MLP) chemotaxis by PMNLs incubated with 10 or 30 micrograms/ml niflumic acid (35 or 106 nmol/ml) or Cu(II)2(niflumate)4 (8 or 23 nmol/ml) were significantly (p < 0.01 to p < 0.001) decreased in dose-related fashions. Chemotaxis of PMNLs from pleuritic rats treated orally with 10 or 30 mg/kg niflumic acid or Cu(II)2(niflumate)4 was significantly (p < 0.001) inhibited by the larger dose of niflumic acid and both doses of Cu(II)2(niflumate)4. Opsonized zymosan (OZ)-stimulated chemiluminescence (CL) of PMNLs from pleuritic rats treated orally with these same doses of niflumic acid or Cu(II)2(niflumate)4 was only significantly (p < 0.05 or p < 0.01 respectively) decreased by the larger doses. Superoxide (O2-) production by these cells was significantly decreased by the larger dose of niflumic acid (p < 0.05) while both doses of Cu(II)2(niflumate)4 produced significant (p < 0.05 to p < 0.01) decreases.(ABSTRACT TRUNCATED AT 250 WORDS)
在同种血清诱导的大鼠胸膜炎中，研究了用四-μ-2-[3-(三氟甲基)-苯基]氨基烟酸二铜(II)[Cu(II)₂(尼氟酸)₄]和尼氟酸治疗产生的抗炎活性及对中性粒细胞（PMNL）反应的调节作用。10或30mg/kg（35或106μmol/kg）的尼氟酸或Cu(II)₂(尼氟酸)₄（8或23μmol/kg）剂量可使胸腔渗出液及渗出液中多形核白细胞（PMNL）数量显著减少（p<0.01）。虽然两种剂量的Cu(II)₂(尼氟酸)₄在这两个参数上均产生显著的剂量相关减少，但只有较高剂量的尼氟酸在这两个参数上产生显著的剂量相关减少。用10或30μg/ml尼氟酸（35或106nmol/ml）或Cu(II)₂(尼氟酸)₄（8或23nmol/ml）孵育的PMNL对N-甲酰甲硫氨酰亮氨酰苯丙氨酸（f-MLP）趋化性的Boyden小室测量结果以剂量相关方式显著降低（p<0.01至p<0.001）。口服10或30mg/kg尼氟酸或Cu(II)₂(尼氟酸)₄治疗的胸膜炎大鼠的PMNL趋化性受到较大剂量的尼氟酸和两种剂量的Cu(II)₂(尼氟酸)₄的显著抑制（p<0.001）。用相同剂量的尼氟酸或Cu(II)₂(尼氟酸)₄口服治疗的胸膜炎大鼠的PMNL经调理酵母聚糖（OZ）刺激的化学发光（CL）仅在较大剂量时显著降低（分别为p<0.05或p<0.01）。较大剂量的尼氟酸使这些细胞的超氧化物（O₂⁻）产生显著降低（p<0.05），而两种剂量的Cu(II)₂(尼氟酸)₄均产生显著降低（p<0.05至p<0.01）。（摘要截短于250字）
