Glycyrrhizin attenuates endotoxin- induced acute liver injury after partial hepatectomy in rats
Glycyrrhizin attenuates endotoxin- induced acute liver injury after partial hepatectomy in rats
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DOI：
10.1590/s0100-879x2007001200007
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发表时间：
2007-12-01
影响因子：
2.3
通讯作者：
Sun, X.
中科院分区：
文献类型：
--
作者：
Tang, B.;Qiao, H.;Sun, X.
大量肝切除术合并感染可引起肝功能障碍，甚至多器官衰竭和死亡。甘草酸已被证明具有抗氧化和抗炎活性。本研究的目的是探讨甘草酸是否能减轻内毒素引起的肝部分切除术后急性肝损伤。雄性Wistar大鼠（6 ~ 8周龄，体重200 ~ 250 g）随机分为三组，每组24只，分别为假药组、生理盐水组和甘草酸组。大鼠肝切除70%后24 h静脉注射脂多糖（LPS）。与生理盐水对照组相比，甘草酸在肝切除术前48小时预先给药3次，间隔24小时，可延长肝部分切除术和LPS注射大鼠的生存时间。与生理盐水对照组相比，甘草酸能减轻肝脏组织学变化，显著降低血清天冬氨酸转氨酶、丙氨酸转氨酶和乳酸脱氢酶水平（LPS注射后1、3、6和9 h各处死6只大鼠）。甘草酸还通过下调caspase-3的表达，抑制细胞色素C从线粒体向细胞质的释放，显著抑制肝细胞凋亡。甘草酸的抗炎活性可能依赖于抑制肿瘤坏死因子- α的释放、髓过氧化物酶活性和核因子- κ B向细胞核的易位。甘草酸还能上调增殖细胞核抗原的表达，提示其可能具有促进LPS损伤肝脏再生的作用。总之，甘草酸可能是一种有效的药物，可以保护肝脏免受内毒素引起的损伤，特别是在大量肝切除术后。
Massive hepatectomy associated with infection induces liver dysfunction, or even multiple organ failure and death. Glycyrrhizin has been shown to exhibit anti-oxidant and anti-inflammatory activities. The aim of the present study was to investigate whether glycyrrhizin could attenuate endotoxin-induced acute liver injury after partial hepatectomy. Male Wistar rats ( 6 to 8 weeks old, weighing 200-250 g) were randomly assigned to three groups of 24 rats each: sham, saline and glycyrrhizin. Rats were injected intravenously with lipopolysaccharide (LPS) 24 h after 70% hepatectomy. Glycyrrhizin, pre-administered three times with 24 h intervals 48 h before hepatectomy, prolonged the survival of rats submitted to partial hepatectomy and LPS injection, compared with saline controls. Glycyrrhizin was shown to attenuate histological hepatic changes and significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase, at all the indicated times ( 6 rats from each were sacrificed 1, 3, 6, and 9 h after LPS injection), compared with saline controls. Glycyrrhizin also significantly inhibited hepatocyte apoptosis by down-regulating the expression of caspase-3 and inhibiting the release of cytochrome C from mitochondria into the cytoplasm. The anti-inflammatory activity of glycyrrhizin may rely on the inhibition of release of tumor necrosis factor-alpha, myeloperoxidase activity, and translocation of nuclear factor-kappa B into the nuclei. Glycyrrhizin also up-regulated the expression of proliferating cell nuclear antigen, implying that it might be able to promote regeneration of livers harmed by LPS. In summary, glycyrrhizin may represent a potent drug protecting the liver against endotoxin-induced injury, especially after massive hepatectomy.