CAJ | 학술논문

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、48 h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10 d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,36 h达峰值,48 h有所下降,但仍高于假手术组(P均<0.01);肺组织MIF mRNA和蛋白表达自12 h起即明显增加,之后逐渐增加至48 h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10 d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.
목적 관찰거서세포이동억제인자(MIF)재농독증소서혈청화폐조직중적표체급MIF길항제ISO-1대농독증소서존활솔적영향.방법 용맹장결찰천공술(CLP)건립농독증BALB/c소서모형.40지소서수궤분위가수술조급CLP후12、24、36、48 h조,각취8지소서심장혈,채용매련면역흡부법(ELISA)검측혈청MIF수평,채용역전록-취합매련반응(RT-PCR)、단백질면적인적법(Western blotting)검측폐조직중MIF적mRNA화단백표체.령선택40지소서제비농독증모형,관찰용ISO-1간예후농독증소서10 d적존활솔.결과 여가수술조비교,농독증소서혈청MIF수평축점승고,36 h체봉치,48 h유소하강,단잉고우가수술조(P균<0.01);폐조직MIF mRNA화단백표체자12 h기즉명현증가,지후축점증가지48 h체봉치(P<0.05혹P<0.01).사용MIF길항제ISO-1적농독증조소서10 d존활솔위60%(12/20),교농독증대조조25%(5/20)명현승고(P<0.05).결론 MIF가능작위만기염증세포인자삼여농독증소서적발병과정,사용MIF길항제ISO-1능제고농독증소서적존활솔,제시MIF가작위농독증치료적파향.
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.