SAA与脓毒症进程的相关性及其生物学意义

Relationship between SAA and sepsis and its biological significance

目的通过蛋白质组方法研究CLP模型小鼠,研究脓毒症进程相关的生物标志分子。方法 85只小鼠,分成模型组和假手术组,制作小鼠CLP脓毒症模型,观察脓毒症发生发展的自然过程,同时在关键时间点采用i TRAQ法检测和鉴定血清蛋白,确定与脓毒症进程密切相关的关键分子,并通过q PCR法观察不同组织的mRNA表达,判断其组织来源。结果生存曲线显示,脓毒症小鼠发病12～32 h是死亡发生的关键时间,度过这一时间则进入自然康复期。同时发现一组蛋白在出现、高峰和恢复时间上与这一进程匹配。蛋白鉴定证实,这组蛋白包括SAA1和SAA2,两者表达水平相当,表达规律相同。检查不同组织SAA1 mRNA表达发现,肝脏是合成SAA1的主要场所,肝外组织也能合成少量SAA1。脓毒症组小鼠外周血出现单体形态的SAA1和SAA2蛋白。结论 SAA可能具有多种生物学功能,脓毒症外周血血清SAA是SAA1和SAA2的混合物,肝外组织也能够合成一定量的SAA,血清中的单体形态的SAA可以作为脓毒症的生物标志分子。

Objective To study the biomarkers related to sepsis quantitatively and qualitatively with a CLP mice model and proteomic analysis.Methods 85 mice were divided into model group and sham operation group to make a model of CLP sepsis in mice,to observe the natural process of the development of sepsis.At the same time,i TRAQ method was used to detect and identify the serum protein at the critical time point.The key molecules closely related to the process of sepsis were determined,and the expression of mRNA in different tissues was observed by q PCR method.Results The survival curve showed that 12-32 h of sepsis mice was the key time of death,and then went into the natural recovery period.At the same time,a group of proteins were found to match the process in appearance,peak and recovery time.Protein identification confirmed that the proteins included SAA1 and SAA2,and the expression levels were equal.Examination of SAA1 mRNA expression in different tissues revealed that the liver was the main site for the synthesis of SAA1,but extrahepatic tissue was the source of the so-called acute phase response protein SAA1.Conclusions SAA may have a variety of biological functions.The serum SAA detected by conventional methods is a mixture of SAA1 and SAA2,and the extrahepatic tissue is the main source of detected serum SAA,which can be used as a biomarker for sepsis.SAA synthesized in the liver is transported through specific pathways and may be involved in the rehabilitation of sepsis.