Yang Fan, Wang Li-Kun, Li Xun, Wang Lu-Wen, Han Xiao-Qun, Gong Zuo-Jiong
Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Hepatobiliary Pancreat Dis Int. 2014 Jun;13(3):309-15. doi: 10.1016/s1499-3872(14)60044-8.
Acute liver failure (ALF) is a serious clinical syndrome with high mortality. Sodium butyrate has been shown to alleviate organ injury in a wide variety of preclinical models of critical diseases. The aim of this study was to investigate the protective effect of sodium butyrate on ALF in rats.
All rats were randomly divided into control, model and sodium butyrate treatment groups. Except the control group, the rats were induced ALF animal model by subcutaneous injection of human serum albumin+ D-galactosamine+lipopolysaccharide. After induction of ALF, the rats in the treatment group received sodium butyrate (500 mg/kg) at 12-hour or 24-hour time point. Fourty-eight hours after ALF induction, the animals were sacrificed and samples were harvested. Serum endotoxin, high mobility group box-1 (HMGB1), liver function parameters, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were measured. The expression of HMGB1 and nuclear factor-kappa B (NF-kappaB) p65 protein in liver tissue was detected by Western blotting. The histological changes of liver and intestine were examined. The survival duration was also observed.
Serum endotoxin, alanine aminotransferase, HMGB1, TNF-alpha and IFN-gamma were significantly increased and the liver histology showed more severe histopathological injury in the model group compared with the control group (P<0.05). Compared to the model group, sodium butyrate treatment significantly improved the histopathological changes in the liver and intestine, reduced serum endotoxin and inflammatory cytokines, suppressed HMGB1 and NF-kappaB p65 proteins in liver tissue, and prolonged the survival duration regardless of treatment at 12 hours or 24 hours after induction of ALF (P<0.05).
Sodium butyrate protected the liver from toxin-induced ALF in rats. The mechanisms may be due to direct hepatoprotection and decreased intestinal permeability.
急性肝衰竭（ALF）是一种死亡率很高的严重临床综合征。丁酸钠已被证明可减轻多种危重病临床前模型中的器官损伤。本研究的目的是探讨丁酸钠对大鼠急性肝衰竭的保护作用。
将所有大鼠随机分为对照组、模型组和丁酸钠治疗组。除对照组外，大鼠通过皮下注射人血清白蛋白+D-半乳糖胺+脂多糖诱导建立急性肝衰竭动物模型。诱导急性肝衰竭后，治疗组大鼠在12小时或24小时时间点接受丁酸钠（500mg/kg）。急性肝衰竭诱导后48小时，处死动物并采集样本。检测血清内毒素、高迁移率族蛋白B1（HMGB1）、肝功能参数、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）。通过蛋白质免疫印迹法检测肝组织中HMGB1和核因子-κB（NF-κB）p65蛋白的表达。检查肝脏和肠道的组织学变化。还观察了生存时间。
与对照组相比，模型组血清内毒素、丙氨酸转氨酶、HMGB1、TNF-α和IFN-γ显著升高，肝脏组织学显示更严重的组织病理学损伤（P<0.05）。与模型组相比，丁酸钠治疗显著改善了肝脏和肠道的组织病理学变化，降低了血清内毒素和炎性细胞因子，抑制了肝组织中HMGB1和NF-κB p65蛋白，并延长了生存时间，无论在急性肝衰竭诱导后12小时还是24小时进行治疗（P<0.05）。
丁酸钠对大鼠毒素诱导的急性肝衰竭具有肝脏保护作用。其机制可能是由于直接的肝脏保护作用和肠道通透性降低。
