参附注射液预先给药对孕鼠布比卡因中枢神经系统及心脏毒性的影响

Shenfu injectio pretreatment reduces systemic toxicity of bupivacaine in pregnant rats

目的探讨参附注射液对孕鼠布比卡因中枢神经系统及心脏毒性的影响。方法 24 只 SD 大鼠,分为3组(n=8),非妊娠对照组(FC 组)选用动物为雌性大鼠,妊娠对照组(PC 组)和参附预先给药组(SF 组)选用动物为孕龄16～18d 的孕鼠。在静脉泵注布比卡因2mg·kg^(-1)·min^(-1)前30 min,SF 组注射参附注射液10ml·kg^(-1),FC 组和 PC 组给予等量生理盐水。持续监测平均动脉压和心率,记录泵注布比卡因前(泵注前)、大鼠抽搐、心律失常、心搏停止时布比卡因用量。结果 SF 组抽搐、心律失常及心搏停止时布比卡因的剂量均大于 PC 组(P＜0.05或0.01)。PC 组心律失常时布比卡因的剂量低于 FC 组(P＜0.05)。结论妊娠可增加布比卡因心脏的毒性,预先给予参附注射液可减轻静脉注射布比卡因对孕鼠中枢神经系统及心脏的毒性。

Objective To determine if pregnancy affects the toxicity of bupivacaine and to investigate the effect of Shenfu injectio, a preparation of Chinese herbal medicine, on central nervous system and cardiac toxicity of bupivacaine in pregnant rats.Methods Twenty-four SD rats weighing 320-360 g were assigned to 3 groups （ n = 8 each） ： Ⅰ non-pregnant control group, Ⅱ pregnant control group and m Shenfu injectio pretreatment group. The animals were anesthetized with isoflorane （2%-4%）-O2 inhalation which was stopped before bupivacaine infusion was started. Femoral artery was cannulated for MAP monitoring and blood sampling and femoral vein was cannulated for bupivacaine infusion. MAP, HR and ECG were continuously monitored. All animals in the 3 groups received continuous infusion of 5 % bupivacaine at 2 mg· kg^-1·min^-1. In group Ⅲ Shenfu injectio 10 ml· kg^-1 was injected intraperitoneally （IP） 30 min before bupivacaine infusion whereas in the two control groups （group Ⅰ and Ⅱ ） equal volume of normal saline was injected IP instead of Shenfu injectio. The duration between the beginning of bupivacaine infusion and onset of convulsion / arrhythmia （QRS≥90 ms） / asystol was recorded and the amount of bupivacaine infused was calculated. Results There was no significant difference in the amount of bupivacaine causing convulsion and asystol between group Ⅰand Ⅱbut the amount of bupivacaine causing arrhyflunia was significantly larger in group Ⅰ （non-pregnant） than in group Ⅱ （pregnant control group） （ P 〈 0.05）. The amount of bupivacaine causing convulsion, arrhythmia and asystole was significantly larger in Shenfu injectio pretreatment group （group Ⅲ ） than in pregnant control group （ group Ⅱ ） （ P 〈 0.05 or 0.01 ）. Condusion Bupivacaineinduced cardiotoxicity is increased in pregnant rats and Shenfu injectio pretreatmeut can reduce the systemic toxicity of bupivacaine in pregnant rats.