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甘草酸对小鼠伴刀豆球蛋白A诱导的肝损伤的肝保护作用及对诱导型一氧化氮合酶表达的抑制作用。

Hepatic protection by glycyrrhizin and inhibition of iNOS expression in concanavalin A-induced liver injury in mice.

作者信息

Tsuruoka Noriko, Abe Kazuki, Wake Kenjirou, Takata Masaru, Hatta Akira, Sato Tositugu, Inoue Hideo

机构信息

Pharmacological Research Department, Minophagen Pharmaceutical Co., 2-2-3, Komatsubara, Zama, Kanagawa, 228-0002, Japan.

出版信息

Inflamm Res. 2009 Sep;58(9):593-9. doi: 10.1007/s00011-009-0024-8. Epub 2009 Mar 31.

Abstract

OBJECTIVE AND DESIGN

In this study, the possible protective effect of glycyrrhizin (GL), an active compound derived from licorice root, was examined on T cell-mediated liver injury in mice.

MATERIALS AND METHODS

Mice were subjected to liver injury by intravenous injection of concanavalin A (Con A). They had been treated with GL (i.p.) 30 min before the injection. Liver injury was estimated by measuring serum levels of alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST), and by examining liver sections with hematoxylin-eosin staining. Expression of inducible nitric oxide synthase (iNOS) mRNA and protein in the liver was determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting.

RESULTS

Serum transaminases and hepatic iNOS levels increased with time after Con A treatment. Expression of iNOS mRNA in the liver was elevated for up to 8 h, and at 8 h, GL (ED(50): 10.5 mg/kg) suppressed the increases in AST and ALT in response to Con A. An increase in iNOS mRNA expression and protein was inhibited by treatment with GL. Furthermore, GL inhibited cell infiltration and the degeneration of hepatocytes in the liver of Con A-treated mice.

CONCLUSION

The present study suggests that the prevention by GL of Con A-induced hepatitis is due partly to the modulation of hepatic iNOS induction and of degeneration of hepatocytes.

摘要

目的与设计

在本研究中,检测了甘草根中的活性化合物甘草甜素(GL)对小鼠T细胞介导的肝损伤可能的保护作用。

材料与方法

通过静脉注射伴刀豆球蛋白A(Con A)使小鼠遭受肝损伤。在注射前30分钟用GL(腹腔注射)对它们进行治疗。通过测量血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平,并通过苏木精-伊红染色检查肝脏切片来评估肝损伤。通过逆转录聚合酶链反应(RT-PCR)和蛋白质印迹法测定肝脏中诱导型一氧化氮合酶(iNOS)mRNA和蛋白质的表达。

结果

Con A处理后,血清转氨酶和肝脏iNOS水平随时间升高。肝脏中iNOS mRNA的表达在长达8小时内升高,并且在8小时时,GL(半数有效剂量:10.5mg/kg)抑制了Con A诱导的AST和ALT的升高。GL处理抑制了iNOS mRNA表达和蛋白质的增加。此外,GL抑制了Con A处理的小鼠肝脏中的细胞浸润和肝细胞变性。

结论

本研究表明,GL对Con A诱导的肝炎的预防作用部分归因于对肝脏iNOS诱导和肝细胞变性的调节。

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