山莨菪碱对内毒素刺激的巨噬细胞和内皮细胞前列腺素合成的影响

山莨菪碱抑制内毒素对小鼠腹腔巨噬细胞合成PCI₂,TXA₂,及PGF_2α等的刺激作用。巨噬细胞预先经山莨菪碱处理,内毒素刺激的前列腺素合成也受抑制。在³H-花生四烯酸标记的牛主动脉内皮细胞,山莨菪碱也抑制内毒素刺激的³H标记物质的释放和PGI₂的合成。结果提示山莨菪碱在体外抑制内毒素刺激的前列腺素合成,这种作用可能发生在环氧化酶反应或者更可能是在花生四烯酸释放过程。

THE EFFECT OF ANISODAMINE ON ENDOTOXIN-STIMULATED PROSTAGLANDIN SYNTHESIS BY MACROPHAGES AND ENDOTHELIAL CELLS

Anisodamine, an alkaloid isolated from the Chinese herb Anisodas tanguticus and later synthesized, has been used as an antishock drug in China for two decades. This study attempted to determine if anisodamine affects arachidonic acid metabolism in cultured cells. Results indicate that endotoxin-stimulated synthesis of cyclooxygenase products including prostacyclin (measured as 6-keto-PGF_1α), thromboxane A₂ (measured as TXB₂) and prostaglandin F_2α (PGF_2α) in mice peritoneal macrophages was dose-dependently inhibited by anisodamine at dosages of 0.1～0.5 mg/ml, Preincubation of macrophages with anisodamine (0.5 mg/ml) for 2 h significantly decreased subsequent endotoxin-stimulated 6-keto-PGF_1α and TXB₂ production, In ³H-arachidonic acid prelabelled bovine aorta endothelial cells, both the release of ³H-labelled compounds and-production of 6-keto-PGF_1α were inhibited by anisodamine. It is suggested that anisodamine directly inhibited endotoxin-stimulated prostaglandin synthesis by cells in culture and its site of action might be at the cyclooxygenase reaction or, more likely, at the process of deesterification of cellular lipids.