Department of General Surgery, Fifth Affiliated Hospital of Harbin Medical University, Daqing, China.
Surg Today. 2011 Aug;41(8):1075-84. doi: 10.1007/s00595-010-4423-9. Epub 2011 Jul 20.
Hepatic ischemia/reperfusion (HIR) injury is an unavoidable consequence of major liver surgery, during which endotoxemia often takes place. This study aimed to investigate whether matrine has a protective effect against HIR-induced liver injury aggravated by endotoxin.
Wistar rats were subjected to 30 min of HIR followed by lipopolysaccharide (LPS) (0.5 mg/kg) administration. At the indicated time points, six rats from each group (24 rats) were randomly euthanized to collect blood samples and livers.
Preadministration of matrine protected livers from injury induced by HIR+LPS as the histological score, myeloperoxidase activity and malondialdehyde contents, expression of macrophage-inflammatory protein-2, DNA-binding activity of nuclear factor κB, and serum levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, tumor necrosis factor-α, soluble intercellular adhesion molecule-1, and nitric oxide were significantly reduced, and serum levels of interleukin-6 were further increased. HIR+LPS markedly induced cell apoptosis and necrosis, and upregulated the expression of cleaved caspase-3, Fas, and FasL. Matrine significantly reduced cell necrosis, but had a nonsignificant inhibitory effect on cell apoptosis and expression of cleaved caspase-3 and FasL.
Matrine attenuates endotoxin-induced acute liver injury after HIR mainly by its anti-inflammatory and antioxidative activities, and has little inhibitory effect on cell apoptosis.
肝缺血/再灌注(HIR)损伤是大肝手术不可避免的后果,在此期间常发生内毒素血症。本研究旨在探讨苦参碱是否对 HIR 诱导的肝损伤加重的内毒素血症具有保护作用。
Wistar 大鼠接受 30 分钟的 HIR 后给予脂多糖(LPS)(0.5mg/kg)。在指定的时间点,每组 6 只大鼠(24 只大鼠)被随机安乐死以收集血液样本和肝脏。
苦参碱预处理可保护肝脏免受 HIR+LPS 诱导的损伤,肝组织学评分、髓过氧化物酶活性和丙二醛含量、巨噬细胞炎症蛋白-2 的表达、核因子 κB 的 DNA 结合活性、血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、乳酸脱氢酶、碱性磷酸酶、肿瘤坏死因子-α、可溶性细胞间黏附分子-1 和一氧化氮水平显著降低,血清白细胞介素-6 水平进一步升高。HIR+LPS 明显诱导细胞凋亡和坏死,并上调了 cleaved caspase-3、Fas 和 FasL 的表达。苦参碱显著减少了细胞坏死,但对细胞凋亡和 cleaved caspase-3 和 FasL 的表达没有明显的抑制作用。
苦参碱通过其抗炎和抗氧化活性减轻 HIR 后内毒素引起的急性肝损伤,对细胞凋亡的抑制作用较小。