ABSTRACT
Objective To evaluate the effects of limited fluid resuscitation on systemic inflammatory responses in rats with traumatic hemorrhagic shock through comparing with unlimited fluid resuscitation.Methods Sixty pathogen-free male Sprague-Dawley rats,aged 2-3 months,weighing 250-290 g,were randomly divided into 6 groups (n =10 each) using a random number table:sham operation group (group S),no fluid resuscitation group (group NF),unlimited fluid resuscitation group (group ULF),limited crystalloid fluid resuscitation group (group LR),and limited colloid fluid resuscitation groups (group LSG and group LHES).Traumatic uncontrolled hemorrhagic shock was induced by withdrawal of blood from the femoral artery at 2.5 mL/100 g over a 20-minute period,followed by tail amputation at 10 min after the end of blood withdrawal.At 10 min after the end of blood withdrawal,fluid resuscitation was performed.Lactated Ringer's solution (ULF and LR groups),4 ％ succinylated gelatin (group LSG),or 6 ％ hydroxyethyl starch 130/0.4 (group LHES) was infused intravenously.The initial infusion rate was 2 ml · kg-1 · min-1.The target MAP was maintained at 50 mm Hg in rats with limited fluid resuscitation,while at 80 mm Hg in rats with unlimited fluid resuscitation.After 60 min of fluid resuscitation,bleeding in the tail was stopped by ligation and fluid infusion was replaced with blood resuscitation.After 60 min of blood resuscitation,180 main of observation was started.At 10 min after catheterization of the femoral artery and vein (T0),10 min after the end of blood withdrawal (T1),the end of fluid resuscitation (T2),the end of blood resuscitation (T3),and the end of observation (T4),arterial blood samples were collected to measure hematocrit (Hct)and concentrations of plasma tumor necrosis factor-alpha (TNF-α),interleukin (IL)-6,and IL-10.Blood samples were collected from the femoral artery at T2 for determination of the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) and activity of nuclear factor-kappaB (NF-κB) in monocytes.The amount of blood loss from the tail and volume of fluid infused were also recorded.Another 120 Sprague-Dawley rats were randomly divided into 6 groups (n =20 each) and resuscitation was performed according to the method previously described.The rats were observed for 72 h survival rate.Results Compared with group S,Hct was significantly decreased,the concentrations of plasma TNF-α,IL-6,and IL-10 and activity of NF-κB were increased,and the expression of TLR4,and MyD88 in monocytes was up-regulated in the other groups (P ＜ 0.05).Compared with group NF,the concentrations of plasma TNF-α and IL-6 and NF-κB activity were significantly increased,and the concentration of plasma IL-10 and Hct were decreased,and the expression of TLR4 and MyD88 in monocytes was up-regulated in ULF,LR and LSG groups,and the concentrations of plasma TNF-α and IL-6 were significantly increased,the concentration of plasma IL-10 and Hct were decreased in group LHES (P ＜ 0.05).Compared with group ULF,the concentrations of plasma TNF-α and IL-6 and NF-κB activity were significantly decreased,the concentration of plasma IL-10 and Hct were increased,the survival rate was higher,the expression of TLR4 and MyD88 in monocytes was down-regulated,and the amount of blood loss from the tail was decreased and the volume of fluid infused was reduced in LSG,LHES and LR groups (P ＜ 0.05).Compared with group LR,the concentrations of plasma TNF-α and IL-6 and NF-κB activity were significantly decreased and the expression of TLR4 and MyD88 in monocytes was down-regulated (P ＜ 0.05),and no significant change was found in the concentration of plasma IL-10 in group LHES (P ＞ 0.05),and the volume of fluid infused was reduced and the survival rate was increased (P ＜ 0.05),and no significant change was found in the amount of blood loss from the tail in LSG and LH-ES groups (P ＞ 0.05).Conclusion Compared with unlimited fluid resuscitation,limited fluid resuscitation exerts less effect on systemic inflammatory responses in rats with traumatic hemorrhagic shock,especially when resuscitation with 6％ hydroxyethyl starch 130/0.4 is performed,and inhibition of TLR4/NF-κB signaling pathway is involved in the mechanism.
ABSTRACT
Objective The purpose of this study was to investigate the role of p38 mitogen-activated protein kinase ( p38 MAPK) in the lung injury induced by mechanical ventilation.Methods Fifteen healthy 80 day-old pigs weighing (22.5 ? 1.5)kg were randomly divided into three groups according to the tidal volume(VT) and PEEP of mechanical ventilation: group A (VT = 16ml?kg-1, PEEP = 0) ; group B (VT = 6 ml?kg-1, PEEP= 16cm H2O) and group C(VT = 16ml?kg-1, PEEP = 8cm H2O). The animals were mechanically ventilated for 3h, then sacrificed by exsanguination. Right lower lobe was immediately removed for identification of intercellular adhesion molecule-1 ( ICAM-1 ) expression using immunohistological technique, determination of phosphorylated p38 MAPK content using Western Blot and microscopic examination. Results There was significant histological changes in the lung tissue in group A and B, but no significant histological changes were found in group C. The expression of ICAM-1 was positive in the lung in group A and B but negative in group C. The level of phosphorylated p38 MAPK among the 3 groups. Conclusion Acute lung injury can be induced by mechanical ventilation with high tidal volume or low tidal volume plus high PEEP, p38 MAPK may mediate the inflammatory response-induced lung injury.