Glucan phosphate attenuates cardiac dysfunction and inhibits cardiac MIF expression and apoptosis in septic mice

被引:40
作者
Ha, Tuanzhu
Hua, Fang
Grant, Daniel
Xia, Yeling
Ma, Jing
Gao, Xiang
Kelley, Jim
Williams, David L.
Kalbfleisch, John
Browder, I. William
Kao, Race L.
Li, Chuanfu
机构
[1] E Tennessee State Univ, Dept Surg, Johnson City, TN 37614 USA
[2] E Tennessee State Univ, Dept Internal Med, Johnson City, TN 37614 USA
[3] E Tennessee State Univ, Sect Med Educ, Johnson City, TN 37614 USA
[4] Nanjing Univ, Anim Model Res Ctr, Nanjing 210008, Peoples R China
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2006年 / 291卷 / 04期
关键词
cardiac function; phosphoinositide 3-kinase/Akt signaling; migration inhibition factor;
D O I
10.1152/ajpheart.01264.2005
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
Myocardial dysfunction is a major consequence of septic shock and contributes to the high mortality of sepsis. We have previously reported that glucan phosphate (GP) significantly increased survival in a murine model of cecal ligation and puncture (CLP)-induced sepsis. In the present study, we examined the effect of GP on cardiac dysfunction in CLP-induced septic mice. GP was administered to ICR/HSD mice 1 h before induction of CLP. Sham surgically operated mice served as control. Cardiac function was significantly decreased 6 h after CLP-induced sepsis compared with sham control. In contrast, GP administration prevented CLP-induced cardiac dysfunction. Macrophage migration inhibitory factor (MIF) has been implicated as a major factor in cardiomyocyte apoptosis and cardiac dysfunction during septic shock. CLP increased myocardial MIF expression by 88.3% (P < 0.05) and cardiomyocyte apoptosis by 7.8-fold (P < 0.05) compared with sham control. GP administration, however, prevented CLP-increased MIF expression and decreased cardiomyocyte apoptosis by 51.2% (P < 0.05) compared with untreated CLP mice. GP also prevented sepsis-caused decreases in phospho-Akt, phospho-GSK-3 beta, and Bcl-2 levels in the myocardium of septic mice. These data suggest that GP treatment attenuates cardiovascular dysfunction in fulminating sepsis. GP administration also activates the phosphoinositide 3-kinase/Akt pathway, decreases myocardial MIF expression, and reduces cardiomyocyte apoptosis.
引用
收藏
页码:H1910 / H1918
页数:9
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