ABSTRACT
Recent studies suggested that TLR4 signaling pathways played an important role in the development of LPS-induced acute lung injury (ALI). Sesamin, a sesame lignan exacted from sesame seeds, has been shown to exhibit significant anti-inflammatory activity. The purpose of this study was to investigate the anti-inflammatory effects of sesamin on LPS-induced ALI in mice. Mice ALI model was induced by intratracheal instillation of LPS. Sesamin was given 1 h after LPS challenge. Our results showed that sesamin inhibited LPS-induced lung pathological change, edema, and myeloperoxidase (MPO) activity. Sesamin suppressed LPS-induced inflammatory cytokines TNF-α, IL-6, and IL-1ß production. Furthermore, sesamin inhibited LPS-induced TLR4 expression and NF-κB activation. In conclusion, the results of this study indicated that sesamin protected against LPS-induced ALI by inhibition of TLR4 signaling pathways.
Subject(s)
Acute Lung Injury/drug therapy , Anti-Inflammatory Agents/therapeutic use , Dioxoles/therapeutic use , Lignans/therapeutic use , Toll-Like Receptor 4/metabolism , Animals , Edema/drug therapy , Edema/prevention & control , Enzyme Activation/drug effects , Interleukin-1beta/biosynthesis , Interleukin-6/biosynthesis , Lipopolysaccharides , Lung/pathology , Male , Mice , Mice, Inbred BALB C , NF-kappa B/metabolism , Peroxidase/metabolism , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
Objective To establish a model of multiple trauma combined with uncontrolled hemorrhagic shock so as to provide basis for basic study of multiple trauma.Methods Forty New Zealand male rabbits were equally and randomly divided into four groups,ie,sham group (Group A,with no bloodletting or resuscitation),uncontrolled group (Group B,with bloodletting alone),aggressive fluid resuscitation and limited fluid resuscitation groups (Groups C and D,with bloodletting,hemostasis and resuscitation).Fractures of the right hind limb in rabbits of each group were induced by free drop of a 3 kg hammer from a height of 45 cm.An estimated 30％ of total blood was withdrawn from the right common carotid artery in 20 minutes in bloodletting groups (Groups B,C and D).Successively,the uncontrolled bleeding was caused via acupuncture bloodletting from ileocecal artery branch at 30 minutes in bloodletting groups.Progressive and limited fluid resuscitation using lactated Ringer' s solution (LR) were performed for Groups C and D in the next one hour respectively.Blood transfusion was performed in Groups C and D after ligation of bleeding artery branch at 90 minutes.In addition,LR of three folds more than blood loss was administered in Group D.Survivorship of rabbits in each group was observed at 150 minutes to seven hours.Arterial blood sample was taken at each time point for blood gas analysis and coagulation test.Fracture type,fluid requirements,intra-abdominal blood loss,and rabbits' survival rate at seven hours were recorded.Results Closed comminuted tibiofibular fractures were founded in all groups.Bloodletting groups showed an obvious reduction of MAP,heart rate and pH value and significantly increased levels of K+,blood glucose and lactic acid at 30 minutes (P ＜0.01),whereas MAP and heart rate were returned to baseline level at 150 minutes.Progressive fluid resuscitation significantly increased the intra-abdominal blood loss and fluid requirements (P＜0.01),decreased erythrocrit (P ＜ 0.05),prolonged prothrombin time and activated partial thromboplastin time (P ＜0.05).Survival rate of rabbits was improved significantly by fluid resuscitation at 7 hours (P ＜ 0.01).Conclusion The model is of high stability and reproducibility and therefore is fit for study of multiple trauma combined with uncontrolled hemorrhagic shock.
