氯胺酮-咪唑安定对感染性休克大鼠血清肿瘤坏死因子-α和心肌环磷酸腺苷的影响

Effects of ketamin and midazolam on serum TNF-α and myocardial cAMP in septic shock rats

目的 探讨氯胺酮 (KTM) -咪唑安定 (M )在感染性休克中的作用及可能的作用机制。方法 选择健康、成年SD大鼠 144只 ,随机分为对照组 (NS组、E组 )和试验组 (EM组、EK组、EKM组 )。NS组为正常对照组 ,E组给予内毒素 (LPS) 2 0mg/kg ,ip ,EK组、EKM组、EM组在同E组处理前分别给予KTM 80mg/kgip ,KTM 80mg/kg +M 0 5mg/kgip和M 0 5mg/kgip ,1h后分别追加半剂。溶剂萃取法测血浆E、NE水平 ,放免法测血清TNF α含量及心肌cAMP水平 ,EK、EKM组同时监测KTM血药浓度。结果 使用LPS各组E、NE水平无明显差异 ,E组TNF α显著高于NS组及EK、EKM组 ,cAMP显著低于NS组及EK、EKM组 ;E和EM组及EK和EKM组TNF α、cAMP无差异。结论 氯胺酮有抗感染性休克的作用 ,其机制可能为抑制LPS刺激的TNF α的释放 ,升高心肌cAMP含量 ,保护感染心肌 ;氯胺酮

Objective To explore the effect of ketamine and /or midazolam on serum TNF-α, myocardial cAMP in septic shock and the possible mechanism. Methods 144 healthy and mature Sprague Damley rats of either sex, weighing 180-205g were randomly divided into 5 groups: (A) normal saline (NS),(B) endotoxin (E);(C) endotoxin-midazolam (EM); (D) endotoxin-ketamine and (E) endotoxin-midazolam-ketamine(EMK). Rat model of septic shock was established by injecting intraperitoneally (ip) LPS 20mg/kg according to the method of Fred. Group A and B served as control. In test groups midazolam 0.5mg/kg and/or ketamine 80mg/kg were given ip 20 min before LPS administration, and supplemental half dose (midazolam 0.25mg/kg and/or ketamine 40mg/kg) were given 1 h later. Arterial blood samples were taken for measurements of epinephrine(E),norepinephrine (NE) and TNF-α concentrations. Myocardial tissue was obtained for determination of cAMP level. Survival rate was also recorded. In EK and EKM groups blood ketamine concentration was also checked. Results There were no significant differences in E and NE concentrations between test groups and group E (P>0.05). TNF-α in group EK and EKM was lower than that in group E (P<0.01). Myocardial cAMP level was higher in group EK and EKM than that in group E (P<0.01). There were no differences in TNF-α and cAMP levels between group EM and E or between group EK and EKM (P>0.05). Conclusions Ketamine can inhibit the release of TNF-α caused by LPS and increase myocardial cAMP level, protecting myocardium from sepsis. This may be one of the anti-septic shock mechanisms of ketamine. Combination of midazolam with ketamine does not affect the anti-septic shock property of ketamine.