四氢嘧啶类衍生物ZL-5015抗内毒素作用的实验研究

发布时间：2018-09-11 14:00

【摘要】：目的:探讨1,3-二环戊基-1,2,3,6-四氢嘧啶-4,5-二甲酸二乙酯(ZL-5015)对内毒素攻击小鼠的保护作用及机制。方法:腹腔注射脂多糖(70 mg/kg)制备小鼠内毒素中毒死亡模型和内毒素血症模型。脂多糖(10mg/L)刺激小鼠腹腔巨噬细胞产生炎症相关细胞因子作为体外炎症模型。ELISA法检测细胞白细胞介素1β(IL-1β)、白细胞介素10(IL-10)和肿瘤坏死因子α(TNF-α)的含量。Real-time PCR检测细胞因子mRNA的表达水平。结果:ZL-5015(100和200 mg/kg)预防性灌胃给药能小幅提高内毒素中毒小鼠的存活率和存活时间,在中毒早期能降低内毒素血症小鼠血清中IL-1β和TNF-α的水平,提高IL-10的水平。体外实验表明,ZL-5015(10、20和40μmol/L)能抑制内毒素刺激的腹腔巨噬细胞IL-1β和TNF-α蛋白及mRNA的表达,促进IL-10蛋白及mRNA的表达。结论:四氢嘧啶类化合物ZL-5015能提高内毒素中毒小鼠的存活率和存活时间,但作用较弱,其作用机制可能与抑制促炎细胞因子IL-1β和TNF-α、促进抑炎细胞因子IL-10的表达有关。
[Abstract]:Objective: to investigate the protective effect and mechanism of diethyl tetrahydropyrimidine (ZL-5015) on mice exposed to endotoxin. Methods: lipopolysaccharide (70 mg/kg) was injected intraperitoneally to establish death model and endotoxemia model in mice. Lipopolysaccharide (10mg/L) stimulated mouse peritoneal macrophages to produce inflammatory cytokines was used as an in vitro inflammatory model. Elisa was used to detect interleukin 1 尾 (IL-1 尾), interleukin 10 (IL-10) and tumor necrosis factor 伪 (TNF- 伪). Real-time PCR was used to detect the expression of cytokine mRNA. Results the survival rate and survival time of mice induced by endotoxemia were slightly increased by prophylactic administration of 1: ZL-5015 (100,200 mg/kg), and the levels of IL-1 尾 and TNF- 伪 in serum and IL-10 increased in the early stage of intoxication. In vitro experiments showed that ZL-5015 (10 渭 mol/L and 40 渭 mol/L) inhibited the expression of IL-1 尾 and TNF- 伪 protein and mRNA, and promoted the expression of IL-10 protein and mRNA in peritoneal macrophages stimulated by endotoxin. Conclusion: tetrahydropyrimidine compound ZL-5015 can improve the survival rate and survival time of mice poisoned by endotoxin, but its effect is weak. The mechanism may be related to inhibiting the expression of pro-inflammatory cytokines IL-1 尾 and TNF- 伪 and promoting the expression of anti-inflammatory cytokine IL-10.
【作者单位】：南方医科大学药学院;
【基金】：高等学校博士学科点专项科研基金(No.20114433110013)
【分类号】：R965

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