Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, People's Republic of China.
PLoS One. 2014 Feb 3;9(2):e87977. doi: 10.1371/journal.pone.0087977. eCollection 2014.
Ethyl pyruvate (EP), a potent reactive oxygen species scavenger, has been reported to contribute to the inflammatory process. However, the protective effect of ethyl pyruvate on Concanavalin A (Con A)-induced autoimmune hepatitis have not been explored. Thus, the aims of this study are to investigate both the effects of ethyl pyruvate and its mechanism of protection on Con A-induced autoimmune hepatitis in mice.
Acute autoimmune hepatitis was induced by Con A (20 mg/kg) in Balb/C mice; ethyl pyruvate (40 mg/kg and 80 mg/kg) was administrated 1h prior to the Con A injection. At 3h, 6h and 24h post Con A injection, histological grading, proinflammatory cytokine levels and nuclear factor kappa B (NF-κB) activity were determined.
Following Con A challenge, cytokines TNF-α, IL-2, IL-1β and IL-6 were expressed at 3h and 6h, and the level of HMGB1 significantly increased by 24h. Pretreatment with ethyl pyruvate ameliorated the pathological effects of Con A-induced autoimmune hepatitis and significantly decreased the levels of TNF-α, IL-2, IL-6 and IL-1β at 3h and 6h and the level of HMGB1 at 6h and 24h post injection. Ethyl pyruvate blocked the degradation of IκB α and IκB β and decreased the expression of NF-κB at 24h.
Taken together, these results indicated that ethyl pyruvate protected against Con A-induced autoimmune hepatitis by decreasing both early (TNF-α, IL-2, IL-1β and IL-6) and late (HMGB1) cytokine expression in mice. The reduction of HMGB1 may correlate with the amelioration of NF-κB activity.
已报道,丙酮酸乙酯(EP)作为一种有效的活性氧物质清除剂,可促进炎症反应。然而,丙酮酸乙酯对伴刀豆球蛋白 A(Con A)诱导的自身免疫性肝炎的保护作用尚未得到探索。因此,本研究旨在探讨丙酮酸乙酯对 Con A 诱导的自身免疫性肝炎的影响及其保护机制。
在 Balb/C 小鼠中用 Con A(20mg/kg)诱导急性自身免疫性肝炎;在注射 Con A 前 1h 给予丙酮酸乙酯(40mg/kg 和 80mg/kg)。在注射 Con A 后 3h、6h 和 24h,测定组织学分级、促炎细胞因子水平和核因子 kappa B(NF-κB)活性。
在 Con A 攻击后,TNF-α、IL-2、IL-1β 和 IL-6 在 3h 和 6h 时表达,HMGB1 的水平在 24h 时显著增加。丙酮酸乙酯预处理可改善 Con A 诱导的自身免疫性肝炎的病理效应,并显著降低 TNF-α、IL-2、IL-6 和 IL-1β 在 3h 和 6h 时的水平以及 HMGB1 在 6h 和 24h 时的水平。丙酮酸乙酯阻断了 IκBα和 IκBβ的降解,并降低了 NF-κB 在 24h 时的表达。
综上所述,这些结果表明,丙酮酸乙酯通过降低小鼠早期(TNF-α、IL-2、IL-1β 和 IL-6)和晚期(HMGB1)细胞因子的表达,对 Con A 诱导的自身免疫性肝炎具有保护作用。HMGB1 的减少可能与 NF-κB 活性的改善有关。