七氟醚对失血性休克/复苏猪心肌损伤的影响

Effect of sevoflurane on myocardial injury induced by hemorrhagic shock and resuscitation in pigs

目的 评价七氟醚对失血性休克/复苏猪心肌损伤的影响.方法 选择巴马小型猪24头,雌雄各半,体重20～ 25 kg,3～5月龄,采用随机数字表法,将其分为3组（n=8）：假手术组（S组）、失血性休克/复苏组（HS/R组）和七氟醚组（Sev组）.HS/R组和Sev组经股动脉放血制备失血性休克模型,维持60 min后回输自体血和乳酸钠林格氏液行容量复苏.Sev组于容量复苏前吸入2％七氟醚30 min.于股动脉穿刺置管后、休克后30 min、容量复苏前、容量复苏后30 min、1.5、2.5及3.5 h时采集动脉血样,测定血清肌酸激酶同工酶（CK-MB）活性和心肌肌钙蛋白Ⅰ（cTnI）的浓度;于容量复苏后3.5 h时取心肌,采用ELISA法检测TNF-d和IL-6的含量,采用Western blot法测定磷酸化信号转导及转录激活因子1（p-STAT1）表达水平,光镜下观察心肌病理学结果.结果 与S组比较,HS/R组和Sev组血清CK-MB活性和cTnI浓度、心肌TNF-α及IL-6含量升高,p-STAT1表达上调（P＜0.05）;与HS/R组比较,Sev组血清CK-MB和cTnI浓度、心肌TNF-α及IL-6含量降低,p-STAT1表达下调（P＜0.05）.Sev组病理学损伤程度较HS/R组明显减轻.结论 七氟醚可减轻失血性休克/复苏猪心肌损伤,其机制与抑制心肌STAT1活性,减轻心肌炎性反应有关.

Objective To evaluate the effect of sevoflurane on myocardial injury induced by hemorrhagic shock and resuscitation （HS/R） in pigs.Methods Twenty-four Bama miniature pigs （12 males, 12 females） , weighing 20-25 kg, aged 3-5 months, were randomly divided into 3 groups （n=8 each） using a random number table： sham operation group （group S） , HS/R group and sevoflurane group （group Sev）.The left and right femoral arteries and right femoral vein were cannulated for blood pressure monitoring, blood-letting, blood sampling and fluid infusion.HS/R was induced by blood-letting maintaining for 1 h, followed by resuscitation with autologous blood reinfusion and infusion of lactated Ringer＇s solution 2 times the volume of the blood withdrawn.The pigs in group Sev were exposed to 2% sevoflurane for 30 min before resuscitation.After cannulation, at 30 min after hemorrhagic shock, before resuscitation, and at 30 min, and 1.5, 2.5 and 3.5 h after resuscitation, blood samples were collected from the femoral artery for determination of creatine kinase-MB （CK-MB） activity and cardiac troponin Ⅰ （cTnI） concentration in serum using an automatic biochemical analyzer.Myocardial specimens were obtained at 3.5 h after resuscitation for detection of tumor necrosis factor-alpha （TNF-ot） and interleukin-6 （IL-6） contents （by ELISA） , and phosphor-signal transducer and activator of transcription 1 （p-STAT1） expression （by Western blot）, and for examination of the pathological changes （with light microscope）.Results Compared with S group , the CK-MB activity and cTnI concentration in serum and contents of TNF-α and IL-6 were significantly increased, and the expression of p-STAT1 was up-regulated in HS/R and Sev groups （P〈0.05）.Compared with HS/R group, the CK-MB activity and cTnI concentration in serum and contents of TNF-α and IL-6 were significantly decreased, and the expression of p-STAT1 was downregulated （P〈0.05） , and the pathological changes of myocardia were alleviated in Sev group.Conclusion Sevoflurane can alleviate HS/R-induced damage to myocardia of pigs, and inhibited STAT1 activity and attenuated inflammatory responses in the myocardium are involved in the mechanism.