烧伤小鼠腹腔巨噬细胞肌醇脂质信号系统变化的实验研究

摘要

Purpose:To further study on the mechanism of abnormal macrophages functional changes postburn, insositol lipid signal system and its effects on TNF secretion by peritoneal macrophages (PM() were observed in severely scalded mice. Method: The activity of PL C (phospholipase C), DAG (diacylglycerol), PKC (protein kinase C), and the alternations of IP3 (inositol-1, 4, 5,-triphosphate), Ca2+ and TNF (tumor necrosis factor) in PM( were measured, and the effects of H-7 (1-(5-isoquinolineslfony1)-2-methylpierazine, a specific PKC inhibitor) and W-7 (N-6-amino-hexyl-5-chloro-1-naphthalenesulfonamide, CaM antagonist) on the production of TNF were also observed. Result: It showed that all above-mentioned parameters changes significantly at 6h,12h,24h postburn. There were remarkable decreases of TNF by using H-7. Conclusion: The results suggested that the inositol lipid signal system of PM( is one of the main signal systems participating in the secretion of TNF, and in this system the DAG-PKC signal pathway showed closer relationship than IP3-Ca2+ in the TNF production.%目的：探讨烧伤导致巨噬细胞功能异常的发生机制。方法：测定了严重烧伤小鼠腹腔巨噬细胞(PMΦ)磷酯酶C(PLC)、甘油二酯(DAG)、蛋白激酶C(PKC)的活性，三磷酸肌醇(IP3)、钙离子(Ca2＋)、TNF的变化，以及PKC抑制剂H-7和钙调素(CaM)拮抗剂W-7对TNF产生的影响。结果：上述所观察的指标在严重烧伤后6hr、12hr、24hr、都发生了非常明显的变化，PKC抑制剂H-7能够显著地抑制TNF的产生。结论：腹腔巨噬细胞肌醇脂质信号系统是促使TNF分泌的主要信号途径之一，在肌醇脂质信号系统中以DAG-PKC的信号途径与TNF分泌关系更为密切。