右美托咪定对心肺复苏大鼠氧化应激反应的保护作用

Effects of dexmedetomidine on oxidative stress response in cardiopulmonary resuscitation rats

目的探讨右美托咪定注射液(DEX)对大鼠心肺复苏(CPR)后氧化应激反应的保护作用及其机制。方法36只SD雄性大鼠随机分为3组,每组12只。假手术组(S组),仅给予麻醉、气管插管和血管穿刺,不行窒息和心肺复苏;心肺复苏组(CPR组)和右美托咪定干预组(DEX组),均采用窒息法制备大鼠心搏骤停模型,行标准心肺复苏,待自主循环恢复(ROSC)后,DEX组即刻给予DEX 50μg/kg缓慢静脉注射,CPR组即刻给予与DEX等量的生理盐水注射。分别在基础状态下及ROSC后3 h、12 h、24 h抽取大鼠动脉血,并测定丙二醛(MDA)水平和超氧化物岐化酶(SOD)活性。结果 S组大鼠均存活至24 h;CPR组大鼠经复苏后有11只恢复自主循环,其中9只存活至24 h;DEX组大鼠经复苏后有10只恢复自主循环,且均存活至24 h。3组大鼠在基础状态下MDA水平和SOD活性差异无显著性(P>0.05)。CPR和DEX组大鼠复苏后其MDA水平逐渐增高,而SOD活性逐渐减低,均于12 h达到最高(低)值。DEX组大鼠在复苏后3 h、12 h、24 h其MDA水平明显低于CPR组大鼠[3 h:(5.56±1.19)nmol/ml比(8.54±1.44)nmol/ml,12 h:(8.13±1.93)nmol/ml比(13.60±2.97)nmol/ml,24 h:(6.36±1.17)nmol/ml比(9.82±1.38)nmol/ml],差异均有统计学意义(均P<0.05);DEX组大鼠在复苏后3 h、12 h、24 h其SOD活性明显高于CPR组大鼠[3 h:(152.50±13.59)U/ml比(135.09±12.97)U/ml,12 h:(124.30±14.58)比(95.45±17.79)U/ml,24 h:(132.50±11.61)比(106.63±9.34)U/ml],差异均有统计学意义(均P<0.05)。结论右美托咪定能够减轻大鼠心肺复苏后氧化应激反应,这一作用可能是通过抑制MDA产生、上调SOD活性实现的。

Objective To investigate the effects of dexmedetomidine（ DEX） on improving systemic oxidative stress response after cardiopulmonary resuscitation（ CPR） in rat model. Methods 36 male SD rats were randomly divided into sham operation group,CPR group and DEX group. In sham operation group,the rats underwent anesthesia,endotracheal intubation and vascular puncture without asphyxia and CPR.Rats cardiac arrest model were made with asphyxia and CPR was done in CPR group and DEX group. Rats of DEX group were injected 50 μg / kg dexmedetomidine immediately after recovery of spontaneous circulation（ ROSC）. Rats of CPR group were injected saline using the same volume of DEX. Blood samples were taken before CPR and 3 h,12 h,24 h after ROSC. The levels of serum malondialdehyde（ MDA） and superoxide dismutase（ SOD） were detected respectively. Results Rats of sham operation group survived for 24 h. 11 rats recovered spontaneous circulation after CPR and then 9 rats survived for 24 h in CPR group. 10 rats recovered spontaneous circulation after CPR and then survived for 24 h in DEX group. Baseline levels of MDA and SOD were respectively no significant difference among three groups. The levels of MDA decreased and reached bottom at 12 h later in CPR group and DEX group,and levels of SOD increased and reached peak at 12 h later in CPR group and DEX group after CPR. The levels of MDA in DEX group were significantly lower than those in CPR group since 3 h after ROSC[3 h（ 5. 56 ± 1. 19） vs.（ 8. 54 ±1. 44） nmol / ml; 12 h：（ 8. 13 ± 1. 93） vs.（ 13. 60 ± 2. 97） nmol / ml,24 h：（ 6. 36 ± 1. 17） vs.（ 9. 82 ± 1. 38） nmol / ml]（ all P 0. 05）. Thelevels of SOD in DEX group were significantly higher than those in CPR group since 3 h after ROSC[（ 3 h：（ 152. 50 ± 13. 59） U / ml vs.（ 135.09 ± 12. 97） U / ml,12 h：（ 124. 30 ± 14. 58） U / ml vs.（ 95. 45 ± 17. 79） U / ml,24 h：（ 132. 50 ± 11. 61） U / ml vs.（ 106. 63 ± 9. 34） U / ml]（ all P 0. 05）. Conclusion DEX can reduce oxidative stress response after cardiopulmonary resuscitation in rat model,and this effect may be achieved by inhibiting the production of MDA and up regulation of SOD activity.