期刊
INTENSIVE CARE MEDICINE
卷 38, 期 1, 页码 128-136出版社
SPRINGER
DOI: 10.1007/s00134-011-2353-7
关键词
Sepsis; MFG-E8; Dose response; Human; Survival
资金
- National Institutes of Health (NIH) [R01GM057468, R01GM053008]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM057468, R01GM053008] Funding Source: NIH RePORTER
Animal milk fat globule-EGF factor 8 (MFG-E8) has been shown to be beneficial in attenuating the inflammatory response in sepsis. In this study, we examined the effect of recombinant human MFG-E8 (rhMFG-E8) in an animal model of sepsis in an effort to develop it as a potential therapy against sepsis in humans. Rats were subjected to sepsis by cecal ligation and puncture (CLP), and at 5 h post-CLP, they were given different doses of rhMFG-E8 (20, 40, 80, 160 mu g/kg BW) in normal saline. At 20 h post-CLP, samples were collected for further analysis. A 10-day survival study was also performed. At 20 h after CLP, organ injury indicators, serum IL-6 and TNF-alpha, and plasma HMGB-1 levels were significantly increased as compared to sham-operated animals. Treatment with 20 mu g/kg rhMFG-E8 significantly reduced these levels. With higher doses, further reductions in AST and ALT (59-62%), creatinine (65-68%), and lactate (46-57%), and serum IL-6 and TNF-alpha were obtained. The 160 mu g/kg dose produced the greatest reduction in serum TNF-alpha. With treatment with 20 mu g/kg rhMFG-E8, HMGB-1 levels decreased by 80%, returning back to sham values. In a 10-day survival study, vehicle-treated animals produced a 36% survival rate, while rhMFG-E8 significantly improved the survival rate to 68-72%. Treatment with increasing doses of rhMFG-E8 significantly reduced the number of apoptotic cells detected and markedly attenuated the tissue damages observed in the lungs. These data suggest that recombinant human MFG-E8 is beneficial in ameliorating sepsis in an animal model of sepsis.
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