人参皂甙Rd注射液对大鼠布比卡因中枢及心脏毒性的影响

Effect of ginsenoside-Rd injection on central nervous system and cardiac toxicities of bupivacaine in rats

目的:探讨人参皂甙Rd注射液对大鼠布比卡因中枢及心脏毒性作用的影响。方法:30只雄性SD大鼠,随机分为3组(每组n=10):对照组(C组)、人参皂甙Rd组(R组)和溶剂组(S组)。以肢体Ⅱ导联监测心电图(ECG),暴露大鼠股动脉,置入24G套管针监测动脉血压和准备抽取血样,同时暴露大鼠股静脉,置入24G套管针泵入布比卡因,记录各基础参数后,开始用微量泵泵入5 g/L布比卡因2 mg/(kg.min),密切观察动物,记录其发生抽搐、心律失常、平均动脉压(MAP)降至40 mmHg和心跳停搏的时间,并计算布比卡因总用剂量。结果:泵注布比卡因后,各组动物血压均比泵注前升高,心率明显降低,但组间无统计学差异。MAP降至40 mmHg时,R组动脉血气氧分压(PaO2)为(22±7)kPa,明显高于C组(10±5)kPa。局麻药中毒出现抽搐、心律失常、MAP降至40 mmHg及心跳停搏时R组的布比卡因用量分别为:(17.4±1.6)mg/kg、(18.1±5.2)mg/kg、(30.0±5.0)mg/kg和(40.3±6.6)mg/kg,明显大于相应的C组布比卡因用量:(13.8±1.3)mg/kg、(13.4±4.7)mg/kg、(24.2±5.8)mg/kg和(32.0±6.6)mg/kg(均P<0.05),而S组与C组相似。结论:预先给予人参皂甙Rd注射液可明显减轻布比卡因对大鼠的中枢及心脏毒性。

AIM： To study the effect of ginsenoside-Rd injection, a preparation of Chinese herbal medi- cine, on the central nervous system （CNS） and cardiac toxicities of bupivacaine in rats. METHODS ： Thirty male Sprague Dawley rats weighing 280 -320 g were randomly assigned to three groups： control group （ C）, ginsenoside-Rd group （R） and solvent group （S） （ n = 10 each）. Animals in the R group received ginsenoside-Rd injection 30 mg/kg ip 30 rain before iv infusion of bupivacaine, whereas rats in the C and S groups received an equal volume of saline injection or ginsenoside-Rd solvent （propylene glycol）, respectively. Lead II of the electrocardiogram （ECG） was continuously monitored by three needles stuck into the skin of both forelimb extremities and the left hindleg. The femoral artery was cannulated for direct measurement of arterial blood pressure and for drawing blood samples and the femoral vein was cannulated for bupifacaine infusion. After the basic parameters （arterial blood pressure, heart rate and arterial blood gases） were recorded, 0.5% bupivacaine was infused iv at a rate of 2 mg/（kg·min） to both groups until asystole. The times for bupivacaine-produced convulsions, arrhythmia （QRS prolongation in ECG）, circulation collapse （MAP≤0 mmHg） and asystole were determined and the cumulative dose of bupivacaine was calculated at the corresponding timepoints, respectively. RESULTS： MAP values were significantly increased and the HR was significantly decreased after bupivacaine infusion and the occurrence of convulsion and arrhythmia in both groups. No significant difference was seen in the MAP and HR at the corresponding timepoints between groups. When the MAP was 40 mmHg, the arterial P02 in the Rd groups was remarkably higher than in the bupivacaine group （P 〈 0. 05 ）. In the ginsenoside-d group, cumulative doses of bupivacaine that produced convulsion, arrhythmia and circulation collapse were （ 17.4 ± 1.6 ）, （ 18. 1± 5.2） and （30. 0 ± 5.0） mg/kg, respectively, significantly higher than the doses in the control group （ 13.8 ± 1.3 ）, （ 13.4 ± 4. 7 ） and （24. 2 ± 5. 8 ） mg/kg. CONCLUSION ： Pretreatment with ginsenoside-Rd injection reduces the toxicity of bupivacaine to the central nervous and cardiac systems in rats.