期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 165, 期 4, 页码 1433-1446出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/S0002-9440(10)63401-3
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- NHLBI NIH HHS [HL19982, R01 HL019982, HL73750, P01 HL073750] Funding Source: Medline
During the systemic inflammatory state induced by sepsis, the potential for coagulopathy exists because of up-regulation of natural procoagulants and antifibrinolytics, and down-regulation of natural anti-coagulants, with protein C (PC) being a critical example of the latter case. PC functions as an anti-coagulant, profibrinolytic, and anti-inflammatory agent, and, thus, its administration or deficiency may affect the course and outcome of sepsis in patients. in this study, a cecal ligation and puncture model of septic peritonitis was applied to wild-type mice and litter-mates with a targeted heterozygous deficiency of PC (PC+/-) to characterize the importance of a PC-deficiency on polymicrobial sepsis. An enhanced mortality rate was found to accompany a PC deficiency. Plasma cytokines, as well as organ-specific expression of cytokine transcripts, were elevated in PC+/- mice. No signs of severe disseminated intravascular coagulation (DIC) were observed in wild-type or PC+/- mice, as indicated by an increase in fibrinogen levels and the invariability of platelet counts after cecal ligation and puncture. Consumption of coagulation factors was similar in both genotypes and a decrease in the PC mRNA and protein levels was more prominent in PC+/- mice. Renal and organ muscle damage was enhanced in PC+/- mice, as shown by increases in plasma blood urea. nitrogen, creatinine, and creatinine kinase. Hypotension and bradycardia were more enhanced in PC+/- mice dim in wild-type mice, thus provoking a more severe septic shock response. Thus, the hemodynamic role of PC during sepsis is of critical importance to the outcome of the disease.
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