基于分子对接技术探讨丹参治疗肝损伤的作用机制

Mechanism of Radix Salviae Miltiorrhizae in Treatment of Liver Injury Based on Molecular Docking Technology

目的:利用分子对接技术,探讨丹参治疗肝损伤的作用机制。方法:采用中医药化学数据库和Autodock 4.2软件,将丹参中丹酚酸B、丹酚酸D、丹参素、二氢丹参酮、咖啡酸、隐丹参酮和原儿茶醛等成分分别与枯否细胞表面抗原CD14和信号传导与转录激活因子3(signal transducer and activator of transcription,STAT3)进行分子对接。结果:丹酚酸B、丹酚酸D、丹参素、二氢丹参酮、咖啡酸、隐丹参酮和原儿茶醛与CD14结合的自由能分别为-11.207 76、-8.782 20、-9.827 70、-25.928 40、-16.435 26、-26.137 50和-19.906 32 kJ/mol,与STAT3蛋白结合的自由能分别为-8.447 64、-14.302 44、-18.275 34、-28.855 80、-18.860 82、-28.604 88和-15.891 60 kJ/mol。结论:隐丹参酮、二氢丹参酮、原儿茶醛、咖啡酸与CD14具有较小的自由能,结合作用较强;丹参素、二氢丹参酮、咖啡酸、隐丹参酮与STAT3蛋白具有较小的自由能,结合作用较强。提示丹参治疗脂多糖致肝损伤的作用机制可能为其主要成分与CD14及STAT3蛋白具有较强的结合作用,通过作用于表面受体调控枯否细胞细胞激活及下游STAT3调控STAT3通路,从而对损伤的肝脏起到保护和修复作用。本研究为进一步探讨丹参治疗肝损伤的分子机制提供了参考。

OBJECTIVE：To probe into the mechanism of Radix salviae miltiorrhizae in treatment of liver injury based on molecular docking technology.METHODS：By using Chinese Medicine Chemistry Database and Autodock 4.2 software, molecular docking was respectively conducted between salvianolic acid B, salvianolic acid D, tanshinol, dihydrotanshinone, caffeic acid, cryptotanshinone, protocatechualdehyde in Radix salviae miltiorrhizae and CD14 and signal transducer and activator of transcription （STAT3）.RESULTS：The free energy of salvianolic acid B, salvianolic acid D, tanshinol, dihydrotanshinone, caffeic acid, cryptotanshinone, protocatechualdehyde combined with CD14 were respectively -11.20776 kJ/mol ,-8.78220 kJ/mol, -9.82770 kJ/mol, -25.92840 kJ/mol, -16.43526 kJ/mol, -26.13750 kJ/mol and-19.90632 kJ/mol, yet with STAT3 were respectively -8.44764 kJ/mol, -14.30244 kJ/mol, -18.27534 kJ/mol,-28.85580 kJ/mol, -18.86082 kJ/mol, -28.60488 kJ/mol and -15.89160 kJ/mol.CONCLUSIONS：Cryptotan-shinone , dihydrotanshinone , protocatechualdehyde , caffeic acid showed low free energy and high interaction with CD14;and tanshinol , dihydrotanshinone , caffeic acid , cryptotanshinone showed low free energy and high interaction with STAT3.It is indicated that the mechanism of Radix salviae miltiorrhizae in treatment of liver injury induced by LPS are probably related to the combination of main active ingredient with CD 14 and STAT3 protein, through regulating the Kupffer cells and mediating STAT 3 signal pathway to protect and repair the liver .This study provides reference for the further investigation on Radix salviae miltiorrhizae in treatment of liver injury .