The preventive effects of heparin-superoxide dismutase on carbon tetrachloride-induced acute liver failure and hepatic fibrosis in mice
The preventive effects of heparin-superoxide dismutase on carbon tetrachloride-induced acute liver failure and hepatic fibrosis in mice
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肝素超氧化物歧化酶对四氯化碳所致小鼠急性肝衰竭及肝纤维化的预防作用
DOI：
10.1007/s11010-009-0060-2
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发表时间：
2009-07-01
影响因子：
4.3
通讯作者：
Wang, Fengshan
中科院分区：
文献类型：
--
作者：
Liu, Jinfeng;Tan, Haining;Wang, Fengshan
在这项研究中，评估了肝素-超氧化物歧化酶结合物（肝素-SOD）对四氯化碳（CCl4）诱导的急性肝衰竭和肝纤维化的影响。为了研究肝素-SOD 对急性肝衰竭的影响，通过静脉注射将肝素-SOD 给予 CCl4 处理的小鼠。 CCl4处理24小时后测定生化指标，如谷草酰乙酸转氨酶/谷氨酸丙酮酸转氨酶（GOT/GPT）、谷胱甘肽（谷胱甘肽）、乳酸脱氢酶（LDH）和丙二醛（MDA）。 CCl4 诱导的急性肝衰竭的发生改变了氧化还原状态，肝脏 GSH 减少，脂质过氧化产物形成增加，通过肝素-SOD 或肝素 + SOD 治疗可部分恢复正常。与其他组相比，肝素-SOD组急性肝损伤明显减轻（GOT/GPT、MDA活性降低，GSH活性升高）。为了研究肝素SOD对肝纤维化的影响，肝素SOD和CCl4联合腹腔注射，每周两次，持续12周。组织学和肝脏羟脯氨酸检查显示，肝素SOD可以显着阻止肝纤维化的进展。此外，使用实时 PCR 测定转化生长因子-β 1 (TGF-β 1)、金属蛋白酶-2 (MMP-2)、纤连蛋白和胶原蛋白-I 的表达。值得注意的是，第 12 周结束时，CCl4 诱导的小鼠肝脏出现了更大的纤维化以及 TGF-β1、MMP-2、纤连蛋白和 I 型胶原表达。 Heparin-SOD 可以显着减弱 TGF-β1、MMP-2 和胶原蛋白-I 的 mRNA 表达。组织匀浆的蛋白质印迹显示，肝素-SOD 处理也显着降低了 TGF-β1 的蛋白表达。这些结果表明，给予肝素-SOD可能有助于治疗和预防急性肝衰竭和肝纤维化。
In this study, the effects of heparin-superoxide dismutase conjugate (heparin-SOD) on carbon tetrachloride (CCl4)-induced acute liver failure and hepatic fibrosis were evaluated. To investigate the effects of heparin-SOD on acute liver failure, heparin-SOD was administered to CCl4-treated mice by intravenous injection. Biochemical indicators, such as glutamic oxaloacetic transaminase/glutamic pyruvic transaminase (GOT/GPT), GSH (glutathione), lactate dehydrogenase (LDH), and malondialdehyde (MDA) were determined 24 h after CCl4 treatment. The development of CCl4-induced acute liver failure altered the redox state with a decreased hepatic GSH and increased formation of lipid peroxidative products, which were partially normalized by treatment with heparin-SOD or heparin + SOD. Compared with other groups, the acute liver injury of heparin-SOD group was significantly lessened (reduced activities of GOT/GPT, MDA, and increased activities of GSH). To investigate the effects of heparin-SOD on hepatic fibrosis, heparin-SOD and CCl4 were co-administered by intraperitoneal injection twice a week for 12 weeks. Histological and hepatic hydroxyproline examination revealed that heparin-SOD could significantly prevent the progression of hepatic fibrosis. Moreover, real-time PCR was used to determine transforming growth factor-beta 1 (TGF-beta 1), metalloproteinase-2 (MMP-2), fibronectin, and collagen-I expression. Significantly, greater fibrosis and TGF-beta 1, MMP-2, fibronectin, and collagen-I expression were found in the liver of CCl4-induced mice at the end of 12th week. Heparin-SOD could markedly attenuate the mRNA expression of TGF-beta 1, MMP-2, and collagen-I. Western blots of tissue homogenates revealed that the protein expression of TGF-beta 1 was substantially reduce also by heparin-SOD treatment. These results demonstrate that administration of heparin-SOD may be useful in the treatment and prevention of acute liver failure and hepatic fibrosis.