Effect of resuscitation with hypertonic sodium chloride hydroxyethyl starch 40 injection mixed with suberoylanilide hydroxamic acid on oxidative stress responses and histone acetylation in lung tissues in a rat model of lethal hemorrhagic shock after entering high altitude for the first time / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of resuscitation with hypertonic sodium chloride hydroxyethyl starch 40 injection (HSH40) mixed with suberoylanilide hydroxamic acid (SAHA) on oxidative stress responses of lung tissues and histone acetylation in a rat model of lethal hemorrhagic shock after entering high altitude for the first time.Methods Forty-five healthy male Wistar rats,aged 3-4 months,weighing 250-300 g,were transported from the breeding area at altitude 1500 m to the experimental area at altitude 3 780 m.The rats were divided into 3 groups (n=15 each) using a random number tablesham operation group (group Sham),hemorrhagic shock group (group HS),and resuscitation with HSH40 mixed with SAHA group (group HSH/SAHA).Lethal hemorrhagic shock was induced by removing 40％ of blood volume from the left femoral artery at a constant speed within 10 min,followed by removing 15％ of blood volume from the right femoral vein at a constant speed within 50 min.Only cannulation was performed,and the rats received no blood letting or resuscitation in group Sham.The animals were resuscitated via the right femoral artery after successful establishment of the model,SAHA 7.5/Kg dissolved in HSH40 4 ml/kg was infused within 5 min in group HSH+SAHA.Immediately before blood letting,immediately after blood letting and at 3 h after resuscitation (at the time of death for the rats survived less than 3 h),arterial blood samples were obtained for blood gas analysis,and pH value,partial pressure of arterial carbon dioxide (PaCO2),partial pressure of arterial oxygen (PaO2) and arterial oxygen saturation (SaO2) were recorded.The rats were sacrificed after blood samples were collected from the abdominal aorta at 3 h after resuscitation (at the time of death for the rats died within 3 h after resuscitation),and lungs were removed for examination of the pathologic changes which were scored (with a light microscope) and for determination of wet to dry weight ratio (W/D ratio),activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) and expression of histone H3 acetylation at lysine 9 (Ac-H3K9) in lung tissues (by Western blot).Results Compared with group Sham,the lung injury score,W/D ratio and content of MDA were significantly increased,and the activity of SOD was decreased in HS and HSH+SAHA groups,pH value and PaCO2 were significantly decreased and PaO2 and SaO2 were increased immediately after blood letting and at 3 h after resuscitation in group HS,and PaO2 and SaO2 were significantly increased immediately after blood letting and at 3 h after resuscitation,pH value and PaCO2 were decreased immediately after blood letting,and the expression of Ac-H3K9 was up-regulated in group HSH+SAHA (P＜0.05).Compared with group HS,pH value,PaCO2,PaO2 and SaO2 were significantly increased at 3 h after resuscitation,the lung injury score,W/D ratio and content of MDA were decreased,the activity of SOD was increased,and the expression of Ac-H3K9 was up-regulated in group HSH+SAHA (P＜0.05).Conclusion The mechanism by which resuscitation with HSH40 mixed with SAHA exerts lung protection may be related to inhibiting oxidative stress responses and histone acetylation in lung tissues in a rat model of lethal hemorrhagic shock after entering high altitude for the first time.