人参皂苷Rd注射液减轻布比卡因大鼠中枢神经系统及心脏毒性的作用机制

Protective effect of ginsenoside-Rd injection pretreatment on the central nervous system and cardiac toxicities of bupivacaine in rats

目的探讨人参皂苷Rd注射液减轻布比卡因大鼠中枢神经系统及心脏毒性的作用机制。方法 30只雄性SD大鼠,随机分为3组(n=10):对照组(C组)、人参皂苷Rd组(R组)和溶剂组(S组)。以肢体Ⅱ导联监测心电图(electrocardi-ogram,ECG),暴露大鼠股动脉,置入套管针监测动脉血压和备抽取血样。暴露大鼠股静脉,置入套管针,泵入泵注0.5%布比卡因2 mg/(kg.min)前30 min,R组大鼠腹腔注射人参皂苷Rd注射液30 mg/kg,C组和S组大鼠分别注射相同容积生理盐水和Rd溶剂丙二醇。密切观察动物,记录其发生抽搐、心律失常、平均动脉压(mean aortic pressure,MAP)降至40 mmHg和心跳停搏的时间,并计算布比卡因累积剂量,在其泵药前、发生抽搐、MAP降至40 mmHg时分别抽取动脉血1 ml。提取血清,检测不同时间点血清一氧化氮(nitrous oxide,NO)及一氧化氮合成酶(nitric oxide synthase,NOS)活性。结果布比卡因中毒出现抽搐、心律失常、MAP降至40 mmHg及心跳停搏时,R组的布比卡因用量明显大于相应的C组布比卡因用量。泵注布比卡因后,各组动物NOS活性均比泵注前下降,NO活性在抽搐时比泵注前升高,MAP降至40 mmHg时下降至泵注前水平。布比卡因中毒出现抽搐、MAP降至40 mmHg时,R组血清NO及NOS活性均明显高于C组和S组。结论预先给予人参皂苷Rd注射液可明显减轻布比卡因对大鼠的中枢神经系统及心脏毒性,其机制可能是提高NO及NOS活性水平所致。

Objective To study the possible mechanisms of the protective effect of ginsenoside Rd injection, a preparation of Chinese herbal medincine, on the central nervous system（CNS） and cardiac toxicities of bupivacaine in rats. Methods Thirty male Sprague Dawley rats, weighing 280 to 320 g, were randomly assigned to three groups ： control group （C） , ginsenoside Rd group （R） , and solvent group （S） （n = 10 each）. Animals in group R received ginsenoside Rd injection 30 mg/kg intraperitoneally 30 rain before intravenous infusion of bupivacaine whereas rats in group C and S received an equal volume of saline injection or ginsenoside Rd solvent （propylene glycol） , respectively. Lead II in the electrocardiogram （EEG） was continuously monitored. The femoral ar tery was cannulated for direct measurement of arterial blood pressure and for collection of blood samples. After the basic parameters （arterial blood pressure, heart rate, and arterial blood gases） were recorded, 0.5% bupivacaine was infused intravenously at a rate of 2 mg/（kg · rain） into both groups until asystole. The time of bupivacaineproduced convulsions, arrbythmia （QRS prolongation in ECG） , circulation collapse （MAP≤40 mmHg） ,and asystole were determined before the cumulative dose of bupivacaine was calculat ed at the corresponding time points. During bupivacaine infusion, bupivacaine produced convulsions, and circulation collapse （MAP ≤40 mmHg）, I ml blood sample was drawn and the NO and NOS activities were tested. Results In the ginsenoside Rd group, the cumulative doses of bupivacaine thai produced convulsion, arrhythmia and circulation collapse were significantly higher than those in the control group. The NOS activity was significantly decreased and the NO activity was significantly increased after the onset of convul sion in both groups. The NOS and NO activities in group R were both significantly higher than those in group C and group S during con vulsion and circulation collapse. Conclusion Pretreatment with ginsenoside - Rd injection carl remarkably reduce the toxicity of bupi vacaine to the central nervous arid cardiac systems in rats probably by increasing the NO and NOS activity.