牛磺酸对蟾蜍甾烯在心脏组织分布情况的影响  

Effects of Taurine on Cardiac Tissue Distribution of Toadstene

作　　者：于梦 蒋洁君 马宏跃[1] 周婧[1] YU Meng;JIANG Jiejun;MA Hongyue;ZHOU Jing(Nanjing University of Chinese Medicine,Jiangsu Provincial Key Laboratory of High-Tech Research for Formulations/Jiangsu Provincial Collaborative Innovation Center of Chinese Medicine Resources Industrialization Process,Jiangsu Province Key Laboratory of Chinese Medicine Effectiveness and Safety,Nanjing 210023,China;Kunshan Hospital of Traditional Chinese Medicine,Kunshan 215300,China)

机构地区：[1]南京中医药大学,江苏省方剂高技术研究重点实验室/江苏省中药资源产业化过程协同创新中心,江苏省中药药效与安全性重点实验室,江苏南京210023 [2]昆山市中医院,江苏昆山215300

出　　处：《中医药信息》2024年第4期1-6,34,共7页Information on Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81673563,81274199);江苏省方剂高技术研究重点实验室/江苏省中药资源产业化过程协同创新中心资助项目(FJGJS-2015-15,ZDXM-14);江苏省青蓝工程学术带头人项目。

摘　　要：目的:考察牛磺酸(Tau)对蟾蜍甾烯在心脏组织分布情况的影响。方法:16只雄性豚鼠随机分为空白组、模型组(8 mg/kg蟾酥)、牛磺酸低剂量组(8 mg/kg蟾酥+150 mg/kg Tau)和牛磺酸高剂量组(8 mg/kg蟾酥+300 mg/kg Tau),给予相应处理后,采用HPLC-ESI-TOF-MS分析不同给药组蟾蜍甾烯类成分在豚鼠心脏中的摄取情况,进一步采用分子对接技术模拟牛磺酸与目前已知心脏疾病相关靶点蛋白SCN5A结合位点。结果:在模型组心脏中检测到Gtl、Arg、Hel、Tel、Btl、Bul、Rbg、Cbg和Cbt共9种蟾蜍甾烯的原型,在肝、肾中检测到部分可能发生羟基化的代谢产物,牛磺酸各剂量组心脏中也测到相关蟾蜍甾烯的原型化合物,但与模型组相比,牛磺酸各剂量组心脏中蟾蜍甾烯的摄入均显著减少;分子对接模拟牛磺酸与SCN5A结合能为-3.7 kcal/mol,牛磺酸可以与受体氨基酸Glu1225、Arg1306、Arg1309之间氢键相连。结论:牛磺酸可延缓蟾蜍甾烯类成分在靶器官心脏中的摄取,从而降低蟾酥的心脏毒性,推测牛磺酸与SCN5A的结合位点可能是Glu1225、Arg1306、Arg1309,这为中药配伍在心脏疾病治疗中的应用提供了实际的实验依据。Objective:To investigate the effect of taurine(Tau)on the cardiac tissue distribution of toadstene.Methods:Sixteen male guinea pigs were randomly divided into blank group,model group(8 mg/kg toad venom),low dose taurine group(8 mg/kg toad venom+150 mg/kg Tau)and high dose taurine group(8 mg/kg toad venom+300 mg/kg Tau).After corresponding treatment,HPLC-ESI-TOF-MS was used to analyze the uptake of toadstene in the hearts of guinea pigs in different administration groups,and molecular docking technology was further used to simulate the binding site of taurine and SCN5A,a known target protein related to heart disease.Results:Nine types of toadstenes,Gtl,Arg,Hel,Tel,Btl,Bul,Rbg,Cbg and Cbt,were detected in the heart of the model group.Some metabolites that might have been undergone hydroxylation were detected in the liver and kidney.The prototype compounds related to toadstene were also detected in the hearts of the taurine groups,but the intake of toadstene in the heart was significantly reduced compared with the model group.The binding energy of molecular docking simulated taurine and SCN5A was−3.7 kcal/mol,and taurine could be hydrogen bonded to the receptor amino acids Glu1225,Arg1306,Arg1309.Conclusion:Taurine can delay the uptake of toadstene components in the heart of the target organ,thereby reducing the cardiotoxicity of toad venom.It is speculated that the binding check point of taurine and SCN5A may be Glu1225,Arg1306,and Arg1309.This finding provides a practical experimental basis for the application of traditional Chinese medicine compatibility in the treatment of heart diseases.

关 键 词：牛磺酸 蟾蜍甾烯 蟾酥 配伍 

分 类 号：R285.5[医药卫生—中药学]