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灯盏花素对刀豆蛋白A诱导的小鼠免疫性肝损伤的保护作用及其对促炎细胞因子的影响。

The protective action of scutellarin against immunological liver injury induced by concanavalin A and its effect on pro-inflammatory cytokines in mice.

作者信息

Tan Zheng Huai, Yu Ling Hong, Wei Huai Lin, Liu Geng Tao

机构信息

Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100050, China.

出版信息

J Pharm Pharmacol. 2007 Jan;59(1):115-21. doi: 10.1211/jpp.59.1.0015.

Abstract

Scutellarin is a natural compound from a Chinese herb. The purpose of this paper was to study the protective effect of scutellarin on concanavalin A (Con A)-induced immunological liver injury and its effect on liver nuclear factor kappaB (NF-kappaB), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and inducible nitric oxide synthase (iNOS) expression in mice. Mouse liver injury was produced by injection of Con A 25 mg kg-1 via the tail vein. Scutellarin 50 or 100 mg kg-1 was peritoneally administered to mice 9 or 1 h before injection of Con A. The levels of serum alanine aminotransferase (ALT) and asparatate aminotransferase (AST), NO2-/NO3- and TNF-alpha were determined with biochemical kits, and ELISA using Quantikine Mouse TNF-alpha kit according the manufacturer's instructions. Liver lesions were examined by light microscope. The expression of TNF-alpha, IFN-gamma, iNOS and Fas mRNA in the livers was detected by RT-PCR; and the expression of c-Fos, c-Jun, iNOS and IkappaB proteins was measured by Western Blotting. As a result, pretreatment with scutellarin 100 mg kg-1 significantly decreased the serum ALT, AST, NO2-/NO3- and TNF-alpha levels, and also reduced liver lesions induced by Con A. Scutellarin 100 mg kg-1 down-regulated expression of TNF-alpha and iNOS mRNA, and c-Fos, c-Jun and iNOS protein, while scutellarin enhanced the degradation of IkappaB in the livers of mice injected with Con A. The results suggest that scutellarin has a protective action against Con A-induced liver injury in mice, and its active mechanism may be related to the inhibition of the NF-kappaB-TNF-alpha-iNOS transduction pathway.

摘要

灯盏花素是一种源自中草药的天然化合物。本文旨在研究灯盏花素对刀豆蛋白A(Con A)诱导的免疫性肝损伤的保护作用及其对小鼠肝细胞核因子κB(NF-κB)、肿瘤坏死因子α(TNF-α)、干扰素γ(IFN-γ)和诱导型一氧化氮合酶(iNOS)表达的影响。通过尾静脉注射25 mg/kg的Con A诱导小鼠肝损伤。在注射Con A前9或1小时,给小鼠腹腔注射50或100 mg/kg的灯盏花素。使用生化试剂盒测定血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)、NO2-/NO3-和TNF-α的水平,并根据制造商的说明使用Quantikine小鼠TNF-α试剂盒通过酶联免疫吸附测定法(ELISA)进行检测。通过光学显微镜检查肝脏病变。通过逆转录聚合酶链反应(RT-PCR)检测肝脏中TNF-α、IFN-γ、iNOS和Fas mRNA的表达;并通过蛋白质免疫印迹法(Western Blotting)测定c-Fos、c-Jun、iNOS和IkappaB蛋白的表达。结果显示,用100 mg/kg的灯盏花素预处理可显著降低血清ALT、AST、NO2-/NO3-和TNF-α水平,还可减轻Con A诱导的肝脏病变。100 mg/kg的灯盏花素下调TNF-α和iNOS mRNA以及c-Fos、c-Jun和iNOS蛋白的表达,而灯盏花素增强了注射Con A的小鼠肝脏中IkappaB的降解。结果表明,灯盏花素对Con A诱导的小鼠肝损伤具有保护作用,其作用机制可能与抑制NF-κB-TNF-α-iNOS信号转导通路有关。

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