Objective To investigate the effects and mechanisms of pentoxifylline ( PTX )pretreatment on acute lung injury ( ALI) induced by hemorrhagic shock in mice. Methods Ninety mice were randomly divided into three groups, ie. a control group, a hemorrhagic shock group, and a PTX group.Lung histological changes were examined by HE staining. Meanwhile, the wet-to-dry weight ratio ( W/D) and myeloperoxidase ( MPO) activity in lung were measured. The levels of TNF-αand IL-1βin lung homogenatewere measured by ELISA. The expressions of TLR4 mRNA and TLR4 protein in lung were detected by reverse transcription-polymerase chain reaction ( RT-PCR ) and Western blot, respectively. Results Hemorrhagic shock induced obvious ALI changes in lungs of the hemorrhagic shock group. W/D and MPO activity were significantly higher in the hemorrhagic shock group than the control group( P lt; 0. 01) . The expressions of TNF-α, IL-1β, TLR4 mRNA and TLR4 protein were also significantly higher than the control group( P lt;0. 01) . PTX pretreatment could relieve ALI changes induced by hemorrhagic shock, and decrease W/D and MPO activity. The expressions of TNF-α, IL-1β, TLR4 mRNA and TLR4 protein were also decreased by PTX pretreatment. Conclusions PTX pretreatment shows protective effects on ALI afterhemorrhagic shock. Its possible mechanismmay relate to down-regulation of TLR4, thus inhibit the expression of pro-inflammatory cytokins.
ObjectiveTo determine the effects of different volume fluid resuscitation on intestinal injury and the permeability of intestine in hemorrhagic shock rats. MethodsSprague-Dawley male rats(n=72) were randomly equally divided into 4 groups after the model establishment of blood pressure-controlled hemorrhage, 45, 30, and 15 mL/(kg·h) of fluid resuscitation were performed in high dosage of resuscitation(HLR), moderate dosage of resuscitation(MLR), and low dosage of resuscitation(LLR) group respectively, but rats of Sham group didn't accept fluid resuscitation. After resuscitation, ten centimeters ileum was harvested for testing intestinal permeability. Then 6 rats of each group were sacrificed at 24, 48, and 72 hours after fluid resuscitation respectively. Over the specified time interval, blood was collected for testing levels of lactic acid and plasma tumor necrosis factor-α(TNF-α). The ileums of 3 resuscitation groups were obtained for testing the ratio of wet weight to dry weight and observing the histological changes. ResultsAfter resuscitation, the intestinal permeability was higher in HLR group(P<0.05). At 3-8 hours after resuscitation, rats of Sham group were all died, and the other rats of 3 groups were all alive. The level of plasma lactic acid was lower in LLR group than those of other 2 groups at 24 hours(P<0.05). The levels of TNF-α were higher in HLR group than those of other 2 groups at 24, 48, and 72 hours(P<0.05), and at 48 hours, level of TNF-α in LLR group was lower than MLR group(P<0.05). At 24 hours after resuscitation, ratio of intestinal wet weight to dry weight in LLR group was the lowest, and HLR group was the highest(P<0.05). According to the histopathology, intestinal injuries of the 3 groups were tend to be remission with the time, and at 48 and 72 hours after resuscitation, intestinal villus of LLR group appeared to be normal. ConclusionLimited fluid resuscitation of 15 mL/(kg·h) could not only decrease the levels of lactic acid and TNF-α, but also moderate the intestinal permeability and the intestinal injury in early stage after shock and surgery.