Lin Tzu-Yu, Tseng Sheng-Hong, Li Shao-Jung, Chen Jin-Cherng, Shieh Jiann-Shing, Chen Yun
Department of Anesthesiology, Far-Eastern Memorial Hospital, Taipei, Taiwan.
J Trauma. 2009 Feb;66(2):411-7. doi: 10.1097/TA.0b013e31815ebae9.
Endotoxemia usually causes significant morbidity and mortality, and treatment of endotoxemia is often ineffective. The effects of tetrandrine (a bisbenzylisoquinoline alkaloid) on lipopolysaccharide (LPS)-induced endotoxemia were investigated in mice.
The peritoneal macrophages were stimulated with LPS and treated with or without tetrandrine. The amounts of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10 secreted by peritoneal macrophages were measured by enzyme-linked immunosorbent assay. Mice were intraperitoneally injected with LPS to induce endotoxemia and were treated or not treated with oral gavage with 150 mg/kg tetrandrine 1 hour before or after LPS injection. The survival rate of the mice was determined after they were treated with various regiments. The amounts of TNF-alpha, IL-1beta, IL-6, and IL-10 in the serum of the mice were measured by enzyme-linked immunosorbent assay, and the high mobility group box 1 (HMGB1) concentration was studied by Western blot analysis.
Tetrandrine suppressed the LPS-induced increase of TNF-alpha, IL-1beta, and HMGB1 secretion by peritoneal macrophages but did not affect the IL-6 and IL-10 concentrations. The animals treated with tetrandrine either 1 hour before or after LPS injection had a 100% survival rate, which was significantly higher than that of the control group (40%) (p = 0.005). The LPS-induced increase in serum TNF-alpha, IL-1beta, and HMGB1 concentrations was reduced by tetrandrine treatment administered either 1 hour before or after LPS injection (p < 0.0001). In contrast, tetrandrine prolonged the LPS-induced elevation in serum IL-10 concentrations only mildly changed the serum IL-6 concentrations.
Tetrandrine treatment either 1 hour before or 1 hour after LPS injection reduced the mortality rate of the mice with LPS-induced endotoxemia. The effects of tetrandrine on LPS-induced endotoxemia might be related to the suppression of TNF-alpha, IL-1beta, and HMGB1 concentrations.
内毒素血症通常会导致显著的发病率和死亡率，且内毒素血症的治疗往往效果不佳。本研究在小鼠中探究了粉防己碱（一种双苄基异喹啉生物碱）对脂多糖（LPS）诱导的内毒素血症的影响。
用LPS刺激腹腔巨噬细胞，并分别给予或不给予粉防己碱处理。通过酶联免疫吸附测定法测量腹腔巨噬细胞分泌的肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-6和IL-10的量。给小鼠腹腔注射LPS以诱导内毒素血症，并在LPS注射前或后1小时通过灌胃给予或不给予150mg/kg粉防己碱处理。在用不同方案处理后测定小鼠的存活率。通过酶联免疫吸附测定法测量小鼠血清中TNF-α、IL-1β、IL-6和IL-10的量，并通过蛋白质印迹分析研究高迁移率族蛋白B1（HMGB1）的浓度。
粉防己碱抑制了LPS诱导的腹腔巨噬细胞TNF-α、IL-1β和HMGB1分泌的增加，但不影响IL-6和IL-10的浓度。在LPS注射前或后1小时用粉防己碱处理的动物存活率为100%，显著高于对照组（40%）（p = 0.005）。在LPS注射前或后1小时给予粉防己碱处理可降低LPS诱导的血清TNF-α、IL-1β和HMGB1浓度的升高（p < 0.0001）。相比之下，粉防己碱仅轻微延长了LPS诱导的血清IL-10浓度升高，对血清IL-6浓度影响不大。
在LPS注射前或后1小时给予粉防己碱处理可降低LPS诱导的内毒素血症小鼠的死亡率。粉防己碱对LPS诱导的内毒素血症的作用可能与抑制TNF-α、IL-1β和HMGB1浓度有关。
