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苦参碱减轻大鼠肝缺血/再灌注后内毒素诱导的急性肝损伤。

Matrine attenuates endotoxin-induced acute liver injury after hepatic ischemia/reperfusion in rats.

机构信息

Department of General Surgery, Fifth Affiliated Hospital of Harbin Medical University, Daqing, China.

出版信息

Surg Today. 2011 Aug;41(8):1075-84. doi: 10.1007/s00595-010-4423-9. Epub 2011 Jul 20.

Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

目的

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。

方法

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。

结果

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。

结论

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。

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