摘要
本实验从花生四烯酸(AA)代谢途径探讨麝香抗炎作用机理,用14_C标记花生四烯酸(14_C-AA)标记白细胞,观察麝香对大鼠角叉菜胶炎性渗出液中白细胞内AA释放及其代谢酶产物——白三烯B_4(LTB_4)和5-羟基廿碳四烯酸(5-HETE)生成的影响。实验表明,麝香水提物(MWF)浓度为6.25～37.5μg/ml时,抑制AA释放,释放量比对照组减少50～70％,但不抑制LTB_4和5-HETE的生成;MWF浓度加大至80μg/ml时,AA释放增加至对照组的1.5倍,但LTB_4和5-HETE生物合成却分别抑制了66.7％和90％。提示MWF具有抑制磷脂酶A_2(PLA_2)活性的作用,大剂量时又进一步阻断了AA代谢酶,如5-脂氧酶(5-LO),从而抑制了AA的过氧化,减少炎症介质,如LTB_4、5-HETE等的生成。
The present work was designed to further study the mechanism of the anti-inflammatory action of musk from the viewpoint of arachidonic acid (AA) metabolism; 1) effect on AA release; 2) action on leukotriene B4 (LTB4) and 5-HETE biosyntheses.Leukocytes obtained from rat inflammatory exudate by i.p. injection of 1% carrageenan were labelled with 14C-AA at 37℃ for 2 h. The 14C-AA labelled cells were incubated with the water soluble fraction of musk (MWF) and stimulated with calcium ionophore A23187 to release AA. The radioactivity released from the labelled leukocytes was determined as a criterion of AA release.In order to observe the influence of musk on the biosyntheses of LTB4 and 5-HETE, leukocytes were incubated with MWF and AA, and then stimulated with A23187. The LTB4 and 5-HETE produced were determined by RP-HPLC.The results showed that AA release decreased to 50-70% of the control at MWF concentration of 6. 25-37. 5μg/ml. The biosyntheses of LTB4 and 5-HETE were not affected. However, AA release increased to 1.5-fold at the MWF concentration of 400μg/ml. At the same time, biosyntheses of LTB4 and 5-HETE decreased by 66.7 and 90%, respectively, as compared with controls. This result indicates that MWF not only inhibited phospholipase A2 (PLA2) activity, but also prevented AA peroxidation and inhibited LTB4 biosynthesis.These results suggest that inhibition of the AA metabolic pathway may play a major role in the mechanism of the anti-inflammatory action of musk.
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
1992年第5期346-350,共5页
Acta Academiae Medicinae Sinicae
基金
高校博士学科点专项科研基金资助
