摘要
目的观察巨噬细胞移动抑制因子（MIF）在脓毒症小鼠血清和肺组织中的表达及MIF拮抗剂ISO—1对脓毒症小鼠存活率的影响。方法用盲肠结扎穿孔术（CLP）建立脓毒症BALB／c小鼠模型。40只小鼠随机分为假手术组及CLP后12、24、36、48h组，各取8只小鼠心脏血，采用酶联免疫吸附法（ELIsA）检测血清MIF水平，采用逆转录-聚合酶链反应（RT—PCR）、蛋白质免迹印迹法（Western blotting）检测肺组织中MIF的mRNA和蛋白表达。另选择40只小鼠制备脓毒症模型，观察用ISO—1干预后脓毒症小鼠10d的存活率。结果与假手术组比较，脓毒症小鼠血清MIF水平逐渐升高，36h达峰值，48h有所下降，但仍高于假手术组（P均〈0．01）；肺组织MIFmRNA和蛋白表达自12h起即明显增加，之后逐渐增加至48h达峰值（P〈0．05或P〈0．01）。使用MIF拮抗剂ISO-1的脓毒症组小鼠10d存活率为60％（12／20），较脓毒症对照组25％（5／20）明显升高（P〈0．05）。结论MIF可能作为晚期炎症细胞因子参与脓毒症小鼠的发病过程，使用MIF拮抗剂ISO—1能提高脓毒症小鼠的存活率，提示MIF可作为脓毒症治疗的靶向。
Objective To investigate the expression profile of macrophage migration inhibitory factor （MIF） in serum and lung tissues of mice with sepsis, and to explore the effect of MIF antagonist ISO-1 on sepsis in a murine sepsis model. Methods Sepsis was reproduced in 40 mice by cecal ligation and puncture （CLP）. Heart blood was obtained from 8 mice each at 12, 24, 36, 48 hours after CLP. The content of MIF in serum was determined by enzyme linked immunosorbent assay （ELISA）. MIF mRNA and protein expressions in lung tissues of septic mice were assessed by reverse transcription-polymerase chain reaction （RT-PCR） or Western blotting. Another group of 40 mice were selected to investigate the role and the impact of MIF antagonist ISO-1 in septic mice. Results The content of MIF in serum was higher in septic mice than that in sham operation group, and it peaked at 36 hours, and decreased at 48 hours, but still higher than that in sham operation group （all P〈0. 01）. The MIF mRNA and protein expression in lung tissues of septic mice were higher than those in sham operation group, beginning at 12 hours, and peaked at 48 hours （P〈0. 05 or P〈0. 01）. ISO-1, which was the antagonist of MIF, could elevate the surviving rate of animals with sepsis [60% （12/20） vs. 25% （5/20）, P〈0. 05]. Conclusion MIF plays a role as a late mediator in sepsis, with a high expression of MIF in serum and lung tissue. ISO-1 can elevate the surviving rate in murine model of sepsis. It is concluded that MIF could be taken as a potential target of treatment of sepsis.
出处
《中国危重病急救医学》
CAS
CSCD
北大核心
2009年第8期481-484,共4页
Chinese Critical Care Medicine
