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半胱胺改善狼疮易感小鼠与 IL-6 介导体信号相关的心室肥厚。

Cystamine ameliorates ventricular hypertrophy associated with modulation of IL-6-mediated signaling in lupus-prone mice.

机构信息

Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung City, Taiwan.

出版信息

Life Sci. 2013 Apr 9;92(12):719-26. doi: 10.1016/j.lfs.2013.01.027. Epub 2013 Feb 8.

DOI:10.1016/j.lfs.2013.01.027
PMID:23399703
Abstract

AIMS

The aim of this study is to investigate the protective effects of cystamine on lupus-associated cardiac hypertrophy.

MAIN METHODS

Balb/c and lupus-prone NZB/W-F1 mice were individually randomized into sham group (saline, n=16) and cystamine group (n=16). Mice received saline or cystamine (100 mmol in 100 μL saline) by daily intraperitoneal injection for 2 consecutive weeks. Morphological, histological, and biochemical alterations were investigated.

KEY FINDINGS

Cystamine decreased both left ventricular (LV) mass and LV mass/tissue-to-blood ratio (TBR) in NZB/W-F1 mice (p<0.05), whereas slight effects were observed in Balb/c mice. Moreover, cystamine reduced levels of atrial natriuretic peptide (ANP), C-reactive protein (CRP), heart type-fatty acid binding protein (h-FABP), creatine kinase-MB (CK-MB) and IL-6 in LV tissues of NZB/W-F1 mice (p<0.05). Additionally, in LV tissues of NZB/W-F1 mice, suppression of hypertrophic signaling mediated by IL-6 in response to administration of cystamine was revealed, including phosphorylation of MEK5, ERK5, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) (p<0.05).

SIGNIFICANCE

Cystamine alleviated LV hypertrophy in NZB/W-F1 mice as a result of decrease in hypertrophic mediators and suppression of IL-6 mediated hypertrophic signaling.

摘要

目的

本研究旨在探讨胱胺对狼疮相关性心肌肥厚的保护作用。

方法

将 Balb/c 小鼠和狼疮易感 NZB/W-F1 小鼠分别随机分为假手术组(生理盐水,n=16)和胱胺组(n=16)。小鼠每日腹腔注射生理盐水或胱胺(100 μL 生理盐水含 100 mmol),连续 2 周。观察形态学、组织学和生化改变。

主要发现

胱胺降低了 NZB/W-F1 小鼠的左心室(LV)质量和 LV 质量/组织与血液比(TBR)(p<0.05),而对 Balb/c 小鼠的影响较小。此外,胱胺降低了 NZB/W-F1 小鼠 LV 组织中心房利钠肽(ANP)、C 反应蛋白(CRP)、心脏型脂肪酸结合蛋白(h-FABP)、肌酸激酶-MB(CK-MB)和白细胞介素-6(IL-6)的水平(p<0.05)。此外,在 NZB/W-F1 小鼠的 LV 组织中,发现胱胺抑制了 IL-6 介导的肥厚信号,包括 MEK5、ERK5、c-Jun N 端激酶(JNK)和 p38 丝裂原活化蛋白激酶(p38)的磷酸化(p<0.05)。

意义

胱胺通过降低肥大介质和抑制 IL-6 介导的肥大信号,减轻了 NZB/W-F1 小鼠的 LV 肥厚。

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