Experimental study on anti-endotoxin activity of a tetrahydropyrimidine derivative, ZL-5015
10.3969/j.issn.1000-4718.2015.06.030
- VernacularTitle:四氢嘧啶类衍生物 ZL－5015抗内毒素作用的实验研究
- Author:
Xiaohui QIU
;
Jia LIN
;
Chuanlin YU
;
Nana CHEN
;
Linsheng LEI
- Publication Type:Journal Article
- Keywords:
Tetrahydropyrimidine derivative;
Endotoxin;
Interleukin-1β;
Interleukin-10;
Tumor necrosis fac-torα
- From:
Chinese Journal of Pathophysiology
2015;(6):1137-1141
- CountryChina
- Language:Chinese
-
Abstract:
[ ABSTRACT] AIM:To investigate the protective effect of 1, 3-dicyclopentyl-1, 2, 3, 6-tetrahydropyrimidine-4, 5-dicarboxylic acid diethyl ester (ZL-5015) on lethal endotoxin-challenged mice and to explore the underlying mechanism. METHODS:Mouse model of lethal endotoxin challenge and endotoxemia were established by intraperitoneal administration of lipopolysaccharide (LPS) at a dose of 70 mg/kg to the C57BL/6J mice.Mouse peritoneal macrophages stimulated with LPS (10 mg/L) were used as an in vitro inflammatory model.The levels of interleukin-1β( IL-1β) , interleukin-10 ( IL-10) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA).Real-time PCR was used to evaluate the mRNA expression of the cytokines.RESULTS:Prophylactic treatment of the mice with ZL-5015 (100 and 200 mg/kg, ig) slightly increased the survival rate, extended the survival time, decreased the serum levels of IL-1βand TNF-α, and increased the serum level of IL-10 in the early stage of endotoxemia as compared with model group.The results of in vitro study demonstrated that treatment of the endotoxin-stimulated mouse peritoneal macrophages with ZL-5015 (10, 20 and 40μmol/L) inhibited the expression of IL-1βand TNF-αat both mRNA and protein levels but promoted the expression of IL-10 at both mRNA and protein levels.CONCLUSION: The tetrahydropyrimidine derivative ZL-5015 shows a moderate anti-endotoxin effect by increasing the survival rate and extending the survival time of the mice challenged by endotoxin, which may result from inhibition of the expression of pro-inflammatory cytokines such as IL-1βand TNF-α, and promotion of the expression of anti-inflammatory cytokine IL-10.
