FR167653减轻小鼠免疫性肝损伤。

FR167653 attenuates murine immunological liver injury.

作者信息

Yao Hong-Wei, Li Jun, Chen Ji-Qiang

机构信息

Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, School of Medicine, Zhejiang University, Hangzhou 310031, Zhejiang Province, China.

出版信息

World J Gastroenterol. 2004 Aug 1;10(15):2267-71. doi: 10.3748/wjg.v10.i15.2267.

DOI:10.3748/wjg.v10.i15.2267

PMID:15259079

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4724965/

Abstract

AIM

To study the effect of FR167653 on immunological liver injury (ILI) in mice.

METHODS

ILI was established by tail vein injection of 2.5 mg Bacillus Calmette-Guerin (BCG), and 10 d later with 10 mg lipopolysaccharide (LPS) in 0.2 mL saline (BCG plus LPS). Alanine aminotransferase (ALT), aspartate aminotransferase (AST) in sera and malondialdehyde (MDA), glutathione peroxidase (GSHpx) contents in liver homogenates were assayed by spectrophotometry. The levels of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) levels in sera were determined using ELISA. Interleukin-1 (IL-1) produced by peritoneal macrophages was determined by the method of (3)H-infiltrated cell proliferation. The nuclear factor-kappa B (NF-kappaB) p65 in liver tissue was analyzed with reverse transcription polymerase chain reaction (RT-PCR). Liver samples collected were stained with hematoxylin and eosin.

RESULTS

FR167653 (50, 100, 150 mg/kg) could significantly decrease the serum transaminase (ALT, AST) activity and MDA content in liver homogenate, and improve reduced GSHpx level of liver homogenate. Liver histopathological examination showed FR167653 (100, 150 mg/kg) significantly reduced inflammatory cells infiltration and liver cells necrosis. FR167653 (50, 100, 150 mg/kg) significantly lowered TNF-alpha and NO levels in serum, and IL-1 produced by peritoneal macrophages. Moreover, expression of NF-kappaB mRNA in liver tissue of ILI induced by BCG plus LPS was significantly reduced by FR167653.

CONCLUSION

All results showed that FR167653 had significant inhibitory action on ILI in mice.

摘要

目的

研究FR167653对小鼠免疫性肝损伤（ILI）的影响。

方法

通过尾静脉注射2.5mg卡介苗（BCG）建立ILI模型，10天后腹腔注射10mg脂多糖（LPS）溶于0.2mL生理盐水（BCG加LPS）。采用分光光度法检测血清中谷丙转氨酶（ALT）、谷草转氨酶（AST）以及肝匀浆中丙二醛（MDA）、谷胱甘肽过氧化物酶（GSHpx）的含量。采用酶联免疫吸附测定法（ELISA）检测血清中肿瘤坏死因子-α（TNF-α）和一氧化氮（NO）水平。采用³H渗入细胞增殖法检测腹腔巨噬细胞产生的白细胞介素-1（IL-1）。采用逆转录聚合酶链反应（RT-PCR）分析肝组织中核因子-κB（NF-κB）p65。收集的肝脏样本进行苏木精-伊红染色。

结果

FR167653（50、100、150mg/kg）可显著降低血清转氨酶（ALT、AST）活性及肝匀浆中MDA含量，并提高肝匀浆中降低的GSHpx水平。肝脏组织病理学检查显示，FR167653（100、150mg/kg）可显著减少炎性细胞浸润和肝细胞坏死。FR167653（50、100、150mg/kg）可显著降低血清中TNF-α和NO水平以及腹腔巨噬细胞产生的IL-1。此外，FR167653可显著降低BCG加LPS诱导的ILI小鼠肝组织中NF-κB mRNA的表达。