环孢素A对严重创伤失血性休克大鼠的治疗作用

Beneficial effects of Cyclosporin A on traumatic hemorrhagic shock in rats

目的观察环孢素A(CsA)对创伤失血性休克大鼠的治疗作用。方法采用144只健康成年SD大鼠,分为正常对照组、休克对照组、乳酸林格氏液(LR)复苏组、CsA 1 mg/kg、5 mg/kg和10 mg/kg组。建立创伤失血性休克模型后,观察不同剂量CsA治疗对休克动物的存活时间和24 h存活率的影响,同时通过股动脉和左心室插管测定血流动力学指标,观察CsA对大鼠平均动脉血压(MAP)、左心室收缩压(LVSP)、左心室舒张末压(LVEDP)、左心室压力最大上升/下降速率(±dp/dtmax)和心率(HR)的影响。结果 CsA(5 mg/kg和10 mg/kg)可明显提高创伤失血性休克大鼠的存活时间和24 h存活率。休克后大鼠血流动力学指标包括MAP、LVSP、±dp/dtmax和HR都显著降低,LR复苏可使各项指标有所回升,但显著低于正常对照组;CsA(5 mg/kg和10 mg/kg)可明显升高LVSP和±dp/dtmax,在复苏2 h时明显高于LR组,并接近正常水平。结论 CsA显示出较好的抗创伤失血性休克作用,其中以5 mg/kg和10 mg/kg的给药剂量效果明显。

Objective To investigate the beneficial effects of cyclosporin A （CsA） on traumatic hemorrhagic shock in rats. Methods The traumatic hemorrhagic shock model was adopted in 144 SD rats which were divided into 6 groups： sham-operated group, shock control group,lactated Ringer＇s solution （LR） group,CsA 1 mg/kg,5 mg/kg and 10 mg/kg group. The effects of three doses of CsA on the animal survival time and 24 h survival rate were observed, and the effects of CsA on hemodynamic parameters, including mean arterial blood pressure （MAP） , left intraventricular systolic pressure （LVSP） , left ventricular end-diastolic pressure （LVEDP） , maximal change rate of left intraven- tricular pressure （ ± dp/dtmax ） and heart rate （HR） were also observed. Results CsA at the concentration of 5 mg/kg and 10 mg/kg can significantly increase the survival time and 24 h survival rate of shock rats ,the survival rate was increased to 56.3% from 25% of LR group. After shock, the hemodynamic parameters were significantly decreased including MAP, LVSP and ± dp/dtmax, LR infusion only improved the hemodynamics to some extent ,which were significantly lower than those in sham-operated group. CsA （5 mg/kg and 10 mg/kg） can signifi- cantly improve the hemodynamics of shock rats including LVSP and ± dp/dtmax,which were increased at 2 h after resuscitation as comparedto LR group, and return to about normal levels. 1 mg/kg of CsA ＇also restored the hemodynamic parameters, but there were no significant differences between CsA 1 mg/kg group and LR group. Conclusion CsA has good beneficial effect on traumatic hemorrhagic shock, and 5 mg/kg and 10 mg/kg of CsA showed a better effect.