Effects of GM-CSF Gene Transfected BMSCs on Vascular Endothelial Injury,Coagulation Function and Inflammatory Factors in Septic Mice
Objective:To investigate the effects of granulocyte-macrophage colony-stimulating factor(GM-CSF)gene transfected bone marrow mesenchymal stem cells(BMSCs)on vascular endothelial injury,coagulation function and inflammatory factors in septic mice.Methods:60 SD mice were divided into Sham group,model(Model)group,BMSCs group and GM-CSF-BMSCs group,with 15 mice in each group,sepsis model of mice was prepared by cecal ligation and puncture.The expression of GM-CSF gene was detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).The tail bleeding time of 24h mice was recorded.The levels of plasma prothrombin time(PT),activated partial thromboplastin time(APTT),thrombin time(TT)and fibrinogen(Fib)were detected.The levels of serum interleukin(IL)-6,tumor necrosis factor(TNF)-α,IL-1 and IL-10 were detected by ELISA.The morphology of vascular tissue was observed by hematoxylin-eosin(HE)staining.Apoptosis of vascular endothelial cells was detected by TUNEL method.The expression of vascular tissue factor(TF),tissue factor pathway inhibitor(TFPI),antithrombin(ATIII)),vascular cell adhesion molecule 1(VCAM1)and protease-activated receptor 1(PAR1)were detected by Western blot.Results:Compared with BMSCs in CK group,the expression of GM-CSF mRNA in BMSCs in Transfection group was significantly increased(P＜0.05).Compared with Sham group,the vascular morphology of the mice in Model group was significantly damaged,the tail bleeding time,Fib content,serum IL-10 level and ATⅢ protein expression in vascular endothelial tissue of the mice in Model group were significantly decreased,PT,APTT,TT time,serum IL-6,TNF-α,IL-1 levels,apoptosis rate,TF,TFPI,VCAM1,PAR1 protein expression in vascular endothelial tissue were significantly increased(P＜0.05).Compared with Model group,the damage of vascular morphology and structure in BMSCs group and GM-CSF-BMSCs group was significantly reduced,the tail bleeding time,Fib content,serum IL-10 level and ATⅢ protein expression in vascular endothelial tissue were significantly increased,PT,APTT time,serum IL-6,TNF-α,IL-1 level,apoptosis rate,TF,TFPI,VCAM1 and PAR1 protein expression in vascular endothelial tissue were significantly decreased(P＜0.05).The detection indexes in GM-CSF-BMSCs group were better than those in BMSCs group(P＜0.05).Conclusion:GM-CSF transfected BMSCs can reduce the inflammatory response and vascular endothelial cell injury in septic mice,and improve coagulation function.
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