萘磺酰胺衍生物对细菌脂多糖诱导小鼠腹腔巨噬细胞分泌肿瘤坏死因子的影响

研究了6种氯代萘磺酰胺衍生物对细菌脂多糖(LPS)诱导经卡西霉素A₂₃₁₈₇体外激活的巨噬细胞分泌肿瘤坏死因子(TNF)作用的影响。表明:将氯代萘磺酰胺的氨基接以亲水性不同长度碳链的胺基,所得衍生物可明显抑制LPS诱生TNF的作用;接以疏水性烷基,则可明显增强亚适剂量的LPS诱生TNF的作用,且碳链长度对化合物的作用强度有一定的影响。

EFFECTS OF SIX NAPHTHALENESULFONAMIDE DERIVATIVES ON LPS-INDUCED RELEASE OF TUMOR NECROSIS FACTOR FROM MOUSE PERITONEAL MACROPHAGES

The effects of six naphthalenesulfonamide derivatives were studied on the LPS-induced release of tumor necrosis factor (TNF) from mouse peritoneal macrophages primed with A₂₃₁₈₇. The calmodulin (CAM) antagonist, N-( 6- aminohexyl )- 5- chloro- 1- naphthalenesulfonamide (W-7) and its derivatives N-( 6- aminobutyl )- 5- chloro- 1- naphthalenesulfonamide and N- ( 6-aminoethyl)-5-chloro-1-naphthalenesulfonamide (10～400 ng/ml) were found to inhibit LPS-induced TNF release in a dose-dependent manner, and the protein kinase C (PKC) activator, N-(n-heptyl)-5-chloro-1-naphthalenesulfonamide (SC- 10) and its two derivatives, N- ( n- quinyl )- 5-chloro-1-naphthalenesulfonamide and N-(n-butyl )- 5- chloro-1- naphthalenesulfonamide ( 1～16μg/ml) were shown to increase LPS-induced TNF release at suboptimal doses in a dose-dependent manner. These results suggest that the LPS-induced release of TNF is CAM-dependent and PKC may play an important role in this process.