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[摘要]
目的 研究诃子汤炮制草乌对草乌多成分体内动态变化过程的影响,从而探讨蒙医诃子汤炮制草乌机理。方法 采用超高效液相色谱-串联飞行时间/质谱(Ultra performance liquid chromatogr time of flight/mass spectrometry,UPLC-Q-TOF/MS)技术和封闭肠环法,收集生草乌、炮制草乌及诃子的肠壁吸收、肠道菌吸收代谢以及肝代谢样品,分别建立大鼠含药血浆指纹图谱,对各个样品所含成分进行对比分析研究。结果 在肠壁吸收研究中检测出生草乌、炮制草乌成分共32种,其中生草乌组、制草乌组共有成分16种、只在生草乌组检测出而未在制草乌组检测到成分8种、只在制草乌组检测出而未在生草乌组检测出成分8种,诃子成分17种。在肠道菌吸收代谢研究中检测出草乌31种成分,其中生草乌、制草乌组共有成分10种、只在生草乌组检测出而未在制草乌组检测到成分7种、只在制草乌组检测到而未在生草乌组检测出成分14种,诃子13种成分。在肝代谢研究中草乌检测出21种成分,其中生草乌组、制草乌组共有成分5种、只在生草乌组检测出而未在制草乌组检测到成分7种、只在制草乌组检测出而未在生草乌组检测出成分9种,诃子11种成分。对已鉴定出成分进行含量对比研究结果显示生草乌组与制草乌组相比较其成分在肠壁吸收中较多在肠道菌及肝中吸收代谢较少,而制草乌与诃子成分在肠道菌及肝代谢中较多,而在肠壁与肝代谢中较少。结论 经过诃子汤炮制草乌可使草乌成分吸收代谢位点发生了变化,使草乌成分在肠壁吸收中变少而肠道菌及肝代谢中变多。由此可知,经诃子汤炮制使草乌成分的吸收变缓慢且代谢变快,因而可有效起到草乌中毒性成分被人体缓慢吸收且快速代谢。由此推断,诃子汤炮制草乌通过以下途径达到减毒目的:一方面避免草乌毒性成分吸收过快而导致血药浓度快速升高导致中毒;另一方面加速代谢毒性成分,进而降低血药浓度而避免中毒。
[Key word]
[Abstract]
Objective To study the effect of processing Radix Aconiti with Hezi Decoction on the dynamic change process of multi components in Radix Aconiti, so as to explore the mechanism of processing Radix Aconiti with Mongolian medicine Hezi Decoction.Methods UPLC-Q-TOF /MS technique and closed intestinal ring method were used to collect the intestinal wall absorption, intestinal bacteria absorption and metabolism and liver metabolism samples of aconite and processed aconite and Hezi. The medicated serum fingerprint was established, and the components contained in each sample were compared and analyzed.Results In the study of intestinal wall absorption, 32 components of Radix Aconiti were detected, including 16 components in both raw Radix Aconiti group and processing Radix Aconiti group, 8 components only in raw Radix Aconiti group but not in processing Radix Aconiti group, 8 components only in processing Radix Aconiti group but not in raw Radix Aconiti group, and 17 components of Hezi. In the study of intestinal bacteria absorption and metabolism, 31 components of Radix Aconiti were detected, including 10 components in raw Aconitum and processing Aconitum group, 7 components only in raw Aconitum group but not in processing Aconitum group, 14 components only in processing Aconitum group but not in raw Aconitum group, and 13 components of Hezi. In the study of liver metabolism, 21 components of Radix Aconiti were detected, including 5 components in raw Radix Aconiti group and prepared Radix Aconiti group, 7 components only in raw Radix Aconiti group but not in processing Radix Aconiti group, 9 components only in processing Radix Aconiti group but not in raw Radix Aconiti group, and 11 components of Hezi. The contents of the identified components were compared and the results showed that compared with the Radix Aconiti group, the components of Radix Aconiti group are more absorbed in the intestinal wall and less absorbed and metabolized in the intestinal bacteria and liver, the components of processing Radix Aconiti and Hezi were more in intestinal bacteria and liver metabolism, but less in intestinal wall and liver metabolism.Conclusion Radix Aconiti processed by Hezi decoction can change the absorption and metabolism sites of Radix Aconiti, so that the components of Aconiti become less in intestinal wall absorption and more in intestinal bacteria and liver metabolism. It can be seen that the processing of Hezi decoction makes the absorption and metabolism of Aconiti components slow and fast, so it can effectively play the role of slow absorption and rapid metabolism of toxic components of Aconiti by the human body. It can be inferred that the detoxification of Radix Aconiti processed by Hezi decoction can be achieved through the following ways: On the one hand, it can avoid the rapid absorption of toxic components of Aconiti, resulting in the rapid increase of blood drug concentration and poisoning; On the other hand, accelerate the metabolism of toxic components, and then reduce the blood drug concentration to avoid poisoning.
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[基金项目]
国家自然科学基金委员会资助项目地区科学基金项目(81360677):蒙药草乌诃子汤炮制品的有效部位与其消化道内生物转化的相关性研究,负责人:松林;中国中医科学院科技创新工程项目(CI2021A04209):基于药/毒代动力学-多组学结合研究诃子汤炮制草乌“减毒存效”机制与“时-量-效/毒”关系,负责人:图雅;教育部蒙医药研发工程重点实验室开放基金项目(MDK2020021):草乌在蒙药中的特色应用探析及其蒙药中应用安全性评价研究,负责人:策力木格。