The Experimental Study Of Early Immune Response Of Multiple Trauma Regulated By Bone Marrow Mesenchymal Stem Cells

Objectives:to explore the features of immune reponse of femur shaft fracture combined with brain injury rats model influenced by BMSCs and the protection for vital organs by BMSCsMethods:55 Sprague-Dawley male rats weighting 250-300g were divided into 3 groups according to random number table,5 rats for control group,25rats for trauma group,25 rats for trauma and stem-cell-transplanted group.All rats except control group were made models of right femur shaft fracture combined with moderate closed brain injury. Rats of stem-cell-transplanted group were injected from caudal vein with 4x106 BMSCs 5 hours after trauma. On day 1,2,3,5,7 after trauma,arterial blood was collected from 5 rats of each group for the following detection(blood of rats of control group was directly collected without special measurement):plasma IL6,IL-8,IL-10, mean fluorescence intensity (MFI) of MHCâ…¡expression on monocytes and TNFa ex vivo synthesis, serum AST,ALT,Cr,BUN,LDH,CK. For esch rat,wet/dry ratio of lung was also detected. Lungs,livers,hearts and kidneys of rats of control group,of 5 rats of trauma group on 1 day after trauma,of 5 rats of stem-cell-transplanted group on 1 day after trauma were collected for pathological section and HE stain. Through comparing changes of immune index (inflammatory mediator, MHCâ…¡expression on monocytes and TNFa ex vivo synthesis)and pathology and functions of vital organs(pathological section, biochemical indicators,W/D of lung),the regulation of immune reponse of severe trauma rat model and protection of vital organs by BMSCs were analysed.Results: 1.In trauma group plasma IL-6,IL-8 rised significantly after trauma,especially during early observation period. Plasa IL-10 firstly reduced and then rised in an extent. Mean fluorescence intensity (MFI) of MHC II expression on monocytes and TNFa ex vivo synthesis reduced significantly immediately after trauma,reaching to the lowest point an the end of observation period. AST,ALT,BUN,CK reached peaks on day 1 and then reduced gradually. Cr rised after trauma and reached peaks on day 3 and then went down gradually. LDH reached peaks on day 3 and then declined. In the early period of observation,lung W/D rised and got to decline in the late period but still was higher compared to control group. According to pathological sections lungs,livers,hearts and kidneys collected from rats on day 1 after trauma,these vital organs were incurred with acute lesion.analysing pathological sections of lungs,Lung injury scores were obviously higher than in the control group.2.In BMSCs-transplanted group, plasma IL-6,IL-8 were obviously lower than in trauma group.IL-10 dropped down for a short period and then showed an obvious upward trend.In the late observation period, IL-10 was even higher than in control group.Although immune indicaters MHCâ…¡expression on monocytes and TNFa ex vivo synthesis descended fast after trauma, numerical values of which exceeded that of trauma group at the same time point after trauma. During midanaphase, up-regulation of these two indicaters were noticed. Serum biochemical indicators,W/D ratio were less increased than that of trauma group. Tissue damage of vital organs was also alleviated judging from pathological observation.Conclusions:Bone marrow derived mesenchymal stem cells combat hyperinflammation and reverse effectively immunosuppression after severe trauma and protect vital organs.