重组小鼠源MANF对LPS诱导的脓毒症急性肺损伤小鼠转归的作用

Therapeutic outcome of recombinant murine MANF on LPS induced acute septic lung injury in mice

目的:探究重组小鼠源MANF对LPS诱导的脓毒症急性肺损伤小鼠转归的作用及潜在的机制。方法:选取SPF级C57BL/6雄性小鼠,以LPS 15 mg•kg^(-1)单次腹腔注射建立脓毒症小鼠模型,6 h后尾静脉注射重组小鼠源MANF观察72 h内小鼠病死率;同时采用HE染色、TUNEL染色对肺组织的损伤进行评价,并测定肺组织还原型谷胱甘肽(Glutathione,GSH)及丙二醛(Malondialdehyde,MDA)含量。结果:重组小鼠源MANF(750μg•kg^(-1),尾静脉注射)可明显降低脓毒症小鼠24 h内病死率(P<0.05);而且MANF可明显减轻脓毒症小鼠肺组织的炎性细胞浸润、肺泡结构损伤以及凋亡阳性细胞数;同时MANF治疗后脓毒症急性肺损伤小鼠肺组织GSH水平明显增加(P<0.05),MDA水平有所改善但未见明显统计学差异(P>0.05)。结论:重组小鼠源MANF对LPS诱导的脓毒症小鼠急性肺损伤具有明显的保护作用,其机制可能与抑制凋亡、抗氧化应激相关。

Objective:To explore the effect and potential mechanism of recombinant mouse MANF on the outcome of LPS induced acute septic lung injury in mice.Methods:SPF C57BL/6 male mice were selected to establish the acute septic lung injury mice model by a single intraperitoneal injection of LPS 15 mg•kg^(-1).Six hours later,recombinant mouse MANF was injected into the caudal vein to observe the mortality of mice within 72 hours;at the same time,HE staining and TUNEL staining were used to evaluate the injury of lung tissue,and the contents of reduced glutathione(GSH)and malondialdehyde(MDA)in lung tissue were measured.Results:Recombinant mouse MANF(750μg•kg^(-1),caudal vein injection)significantly reduced the mortality within 24 hours(P<0.05);moreover,MANF could significantly reduce the inflammatory cell infiltration,alveolar structural damage and the number of apoptosis positive cells in the lung tissue of septic mice;at the same time,after MANF treatment,GSH level in lung tissue of septic acute lung injury mice significantly increased(P<0.05),MDA level improved,but there was no significant statistical difference(P>0.05).Conclusion:Recombinant mouse MANF has obvious protective effect on LPS induced acute lung injury in sepsis mice,and its mechanism may be related to the inhibition of apoptosis and antioxidant stress.