细胞凋亡
败血症
医学
H&E染色
肺炎
转基因小鼠
肠上皮
程序性细胞死亡
免疫学
肺
上皮
病理
男科
免疫组织化学
内科学
转基因
生物
生物化学
基因
作者
Craig M. Coopersmith,Paul E. Stromberg,William M. Dunne,Christopher G. Davis,Daniel M. Amiot,Timothy G. Buchman,Irene E. Karl,Richard S. Hotchkiss
出处
期刊:JAMA
[American Medical Association]
日期:2002-04-03
卷期号:287 (13): 1716-1716
被引量:264
标识
DOI:10.1001/jama.287.13.1716
摘要
Increased intestinal epithelial apoptosis is present in both human autopsy studies and animal models of sepsis. Whether altering gut apoptosis decreases mortality in sepsis induced by pathogenic bacteria outside the gut is unknown.To determine if decreasing levels of intestinal cell death improves survival in a murine model of Pseudomonas aeruginosa pneumonia-induced sepsis.Prospective study in which transgenic mice that overexpress the antiapoptotic protein Bcl-2 in their intestinal epithelium (n = 25) and control littermates (n = 26) were subjected to intratracheal injection of P aeruginosa.Survival at 7 postoperative days, compared between the 2 groups. Secondary outcomes included quantification of gut epithelial apoptosis.Survival in transgenic mice that overexpress Bcl-2 in the intestinal epithelium was 40% (10/25) compared with 4% (1/26) in control littermates 7 days after intratracheal injection of P aeruginosa (P =.001), with differences in survival noted within 24 hours of surgery. Overexpression of Bcl-2 was associated with a decrease in gut epithelial apoptosis demonstrated by active caspase 3 staining, the terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay, and hematoxylin-eosin staining.In this murine model, inhibiting gut epithelial apoptosis by overexpression of Bcl-2 was associated with a survival advantage in P aeruginosa pneumonia-induced sepsis. These results suggest that intestinal epithelial apoptosis may play a role in sepsis-related mortality.
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