JBP485对刀豆蛋白A诱导的小鼠肝损伤的保护作用。

Protective effect of JBP485 on concanavalin A-induced liver injury in mice.

作者信息

Yang Tao, Wu Jingjing, Wang Changyuan, Liu Qi, Ma Xiaochi, Peng Jinyong, Kaku Taiichi, Liu Kexin

机构信息

College of Pharmacy, Dalian Medical University, Dailian, Liaoning, China.

出版信息

J Pharm Pharmacol. 2009 Jun;61(6):767-74. doi: 10.1211/jpp.61.06.0009.

DOI:10.1211/jpp.61.06.0009

PMID:19505367

Abstract

OBJECTIVES

Cyclo-trans-4-l-hydroxyprolyl-l-serine (JBP485) was first isolated from Laennec (hydrolysate of human placenta). We thought it valuable to clarify the anti-hepatitis molecular mechanism of JBP485 to develop a new oral anti-hepatitis drug.

METHODS

We investigated the hepatoprotective effect of JBP485 on immune-mediated, concanavalin A (Con A)-induced liver injury in mice. Mice were administered JBP485 before and after injection of Con A (10 mg/kg). Eight hours after Con A, the cytosolic enzyme activity (alanine aminotransferase, lactate dehydrogenase) in serum, and the enzyme activity or concentration (superoxide dismutase, maleic dialdehyde, myeloperoxidase, nitric oxide) in liver homogenate were determined. The liver slices were investigated to observe changes in histology. The effect of JBP485 on level of tumour necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1) in liver were detected by immunohistochemistry. Hepatocyte DNA fragmentation was assayed by agarose gel electrophoresis and the transcription of the genes bax and bcl-2 in hepatocytes was determined by reverse transcription-polymerase chain reaction.

KEY FINDINGS

Con A increased the cytosolic and liver homogenate enzyme activity, and the concentrations of ICAM-1 and TNF-alpha, which were significantly inhibited by JBP485 administration. Also, the increase in DNA fragmentation and decrease in bcl-2/bax mRNA induced by Con A administration were significantly inhibited by JBP485.

CONCLUSIONS

These results indicated that immune-mediated liver damage can be prevented by JBP485, and that this is mainly associated with immunomodulatory effects on T cells and adhesion molecules, antioxidation, and inhibition of apoptosis.

摘要

目的

环-反式-4-L-羟基脯氨酰-L-丝氨酸（JBP485）最初是从拉埃内克（人胎盘水解物）中分离出来的。我们认为阐明JBP485的抗肝炎分子机制对于开发一种新型口服抗肝炎药物具有重要价值。

方法

我们研究了JBP485对免疫介导的、刀豆蛋白A（Con A）诱导的小鼠肝损伤的保护作用。在注射Con A（10 mg/kg）前后给小鼠施用JBP485。Con A注射8小时后，测定血清中的胞质酶活性（丙氨酸转氨酶、乳酸脱氢酶）以及肝匀浆中的酶活性或浓度（超氧化物歧化酶、丙二醛、髓过氧化物酶、一氧化氮）。观察肝切片的组织学变化。通过免疫组织化学检测JBP485对肝脏中肿瘤坏死因子-α（TNF-α）和细胞间黏附分子-1（ICAM-1）水平的影响。通过琼脂糖凝胶电泳检测肝细胞DNA片段化，并通过逆转录-聚合酶链反应测定肝细胞中bax和bcl-2基因的转录。