Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, China
Hepatobiliary Pancreat Dis Int. 2013 Apr;12(2):180-8. doi: 10.1016/s1499-3872(13)60029-6.
The pathogenesis and progression of acute liver failure (ALF) are closely associated with intestinal endotoxemia because of the high permeability of the intestinal wall. Treatment with ethyl pyruvate (EP) has been shown to protect liver failure effectively. The current study aimed to explore the relationship between proinflammatory cytokines and intestinal permeability, and to investigate whether EP administration might prevent the release of multiple proinflammatory cytokines and decrease intestinal permeability and therefore, protect the liver from injury.
The ALF model was induced by D-galactosamine in rats. The rats were randomly divided into control (saline, i.p.), model (D-galactosamine, 1.2 g/kg, i.p.), prevention [EP injection (40 mg/kg) 2 hours ahead of D-galactosamine] and treatment groups (EP injection 2 hours after D-galactosamine). Samples were obtained at 12 and 24 hours after ALF induction, respectively. The histology of liver and intestinal tissue was assessed. Serum alanine aminotransferase, endotoxin, D(-)-lactate, diamine oxidase (DAO), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and high mobility group box-1 (HMGB1) were evaluated. The survival of rats was also recorded.
The rats in model group showed severe damage to liver tissue and intestinal mucosa 12 and 24 hours after ALF induction. EP significantly improved liver or intestinal injury. In addition, serum endotoxin, D(-)-lactate, DAO, TNF-alpha, IFN-gamma and HMGB1 levels were significantly increased in the model group compared with the control group. There was a positive correlation between intestinal permeability and proinflammatory cytokines. EP significantly reduced serum endotoxin, D(-)-lactate, DAO, TNF-alpha, IFN-gamma and HMGB1 levels. The median survival time was significantly prolonged in both prevention and treatment groups (126 and 120 hours compared with 54 hours in the model group).
EP has protective and therapeutic effects on intestinal mucosa. EP decreases intestinal permeability, and inhibits the release of multiple proinflammatory cytokines in rats with ALF.
由于肠壁通透性高，急性肝衰竭（ALF）的发病机制和进展与肠内内毒素血症密切相关。已证实乙基丙酮酸（EP）的治疗可有效保护肝功能衰竭。本研究旨在探讨促炎细胞因子与肠通透性之间的关系，并研究 EP 给药是否可以防止多种促炎细胞因子的释放，降低肠通透性，从而保护肝脏免受损伤。
采用 D-半乳糖胺诱导大鼠 ALF 模型。将大鼠随机分为对照组（生理盐水，腹腔内注射）、模型组（D-半乳糖胺，1.2 g/kg，腹腔内注射）、预防组[EP 注射（40 mg/kg）在 D-半乳糖胺前 2 小时]和治疗组（D-半乳糖胺后 2 小时 EP 注射）。分别在 ALF 诱导后 12 小时和 24 小时获取样本。评估肝和肠组织的组织学。评估血清丙氨酸氨基转移酶、内毒素、D(-)-乳酸、二胺氧化酶（DAO）、肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）和高迁移率族蛋白 B1（HMGB1）。还记录了大鼠的存活率。
模型组大鼠在 ALF 诱导后 12 小时和 24 小时肝组织和肠黏膜损伤严重。EP 明显改善了肝或肠损伤。此外，与对照组相比，模型组血清内毒素、D(-)-乳酸、DAO、TNF-α、IFN-γ和 HMGB1 水平显著升高。肠通透性与促炎细胞因子呈正相关。EP 显著降低了血清内毒素、D(-)-乳酸、DAO、TNF-α、IFN-γ和 HMGB1 水平。预防组和治疗组的中位存活时间明显延长（与模型组的 54 小时相比，分别为 126 小时和 120 小时）。
EP 对肠黏膜具有保护和治疗作用。EP 降低了 ALF 大鼠的肠通透性，并抑制了多种促炎细胞因子的释放。
