目的测定黄连中的3种生物碱小檗碱、药根碱、巴马汀对痢疾杆菌生长代谢的影响,从热力学角度研究小檗碱类生物碱抑菌作用的量效关系。方法以微量热法测定小檗碱类生物碱作用于痢疾杆菌生长代谢的热谱曲线,并得出相应的热动力学参数,如生长速率常数、产热功率、最大热功率出现时间、抑制率、传代时间等,根据热动力学模型,拟合了3种生物碱产热功率-质量浓度关系,并进行初步的量效关系分析。结果小檗碱、药根碱、巴马汀对痢疾杆菌的生长代谢均有不同程度的抑制作用,在0.08～1.20 mg/mL内随着质量浓度的增加,最大热功率出现时间和传代时间延长,生长速率常数降低和最大产热功率降低,抑制率增加,且与药物质量浓度呈现一定的量效关系。结论 3种生物碱对痢疾杆菌的抑菌活性的强度顺序为小檗碱>巴马汀>药根碱,从热力学角度研究抑菌类中药的量效关系具有定量、灵敏、快速等优势。

Objective To study the effect of berberine,jatrorrhizine,and palmatine in Coptis chinensis on the metabolism of Bacillus shigae and investigate the dose-effect relationship from the view of thermodynamics.Methods By microcalorimetry,the power-time curves of B. shigae growth were obtained and the action on them by addition of berberine,jatrorrhizine,and palmatine at different concentrations in vitro was studied.Meanwhile,the quantitative thermokinetic parameters,such as growth rate constant(k1,k2),maximum heat-output(P1,P2),peak time(t1,t2),inhibition ratio(I),and generation time(tG) obtained from these curves were analyzed and relationship of P-ρ was obtained. Results Results suggested that berberine,jatrorrhizine,and palmatine had different inhibited effects on B.shigae growth in a dose-dependent manner.With the concentration increasing from 0.08 to 1.20 mg/mL, thermokinetic parameters,such as P1,P2,k1,and k2 diminished,I and tG increased.On the contrary,the appearance time of t1 and t2 prolonged.Conclusion Berberine and its analogues have obvious antimicrobial effect and the sequence of antimicrobial activity was berberin palmatine jatrorrhizine.Microcalorimetry is a useful tool to evaluate the dose-effect relationship of antimicrobial drug with its high sensitiviy and significant quantitative information.

“973”计划项目(2007CB512607);国家自然科学基金资助项目(30500665);辽宁省教育厅科研项目计划(L2010334)