中国病理生理杂志
中國病理生理雜誌
중국병리생리잡지
CHINESE JOURNAL OF PATHOPHYSIOLOGY
2015年
6期
1137-1141
,共5页
邱小惠%林嘉%余传林%陈娜娜%雷林生
邱小惠%林嘉%餘傳林%陳娜娜%雷林生
구소혜%림가%여전림%진나나%뢰림생
四氢嘧啶类化合物%内毒素%白细胞介素1β%白细胞介素10%肿瘤坏死因子α
四氫嘧啶類化閤物%內毒素%白細胞介素1β%白細胞介素10%腫瘤壞死因子α
사경밀정류화합물%내독소%백세포개소1β%백세포개소10%종류배사인자α
KEY WORDS] Tetrahydropyrimidine derivative%Endotoxin%Interleukin-1β%Interleukin-10%Tumor necrosis fac-torα
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(10 mg/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。
目的:探討1,3-二環戊基-1,2,3,6-四氫嘧啶-4,5-二甲痠二乙酯(ZL-5015)對內毒素攻擊小鼠的保護作用及機製。方法:腹腔註射脂多糖(70 mg/kg)製備小鼠內毒素中毒死亡模型和內毒素血癥模型。脂多糖(10 mg/L)刺激小鼠腹腔巨噬細胞產生炎癥相關細胞因子作為體外炎癥模型。 ELISA法檢測細胞白細胞介素1β( IL-1β)、白細胞介素10(IL-10)和腫瘤壞死因子α(TNF-α)的含量。 Real-time PCR檢測細胞因子mRNA的錶達水平。結果:ZL-5015(100和200 mg/kg)預防性灌胃給藥能小幅提高內毒素中毒小鼠的存活率和存活時間,在中毒早期能降低內毒素血癥小鼠血清中IL-1β和TNF-α的水平,提高IL-10的水平。體外實驗錶明, ZL-5015(10、20和40μmol/L)能抑製內毒素刺激的腹腔巨噬細胞IL-1β和TNF-α蛋白及mRNA的錶達,促進IL-10蛋白及mRNA的錶達。結論:四氫嘧啶類化閤物ZL-5015能提高內毒素中毒小鼠的存活率和存活時間,但作用較弱,其作用機製可能與抑製促炎細胞因子IL-1β和TNF-α、促進抑炎細胞因子IL-10的錶達有關。
목적:탐토1,3-이배무기-1,2,3,6-사경밀정-4,5-이갑산이을지(ZL-5015)대내독소공격소서적보호작용급궤제。방법:복강주사지다당(70 mg/kg)제비소서내독소중독사망모형화내독소혈증모형。지다당(10 mg/L)자격소서복강거서세포산생염증상관세포인자작위체외염증모형。 ELISA법검측세포백세포개소1β( IL-1β)、백세포개소10(IL-10)화종류배사인자α(TNF-α)적함량。 Real-time PCR검측세포인자mRNA적표체수평。결과:ZL-5015(100화200 mg/kg)예방성관위급약능소폭제고내독소중독소서적존활솔화존활시간,재중독조기능강저내독소혈증소서혈청중IL-1β화TNF-α적수평,제고IL-10적수평。체외실험표명, ZL-5015(10、20화40μmol/L)능억제내독소자격적복강거서세포IL-1β화TNF-α단백급mRNA적표체,촉진IL-10단백급mRNA적표체。결론:사경밀정류화합물ZL-5015능제고내독소중독소서적존활솔화존활시간,단작용교약,기작용궤제가능여억제촉염세포인자IL-1β화TNF-α、촉진억염세포인자IL-10적표체유관。
[ 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.