基于液質(zhì)聯(lián)用技術(shù)的瑞香狼毒化學(xué)成分及藥代動力學(xué)研究
本文選題:瑞香狼毒 + 液質(zhì)聯(lián)用 ; 參考:《河北大學(xué)》2017年碩士論文
【摘要】:瑞香狼毒為瑞香科植物Stellera chamaejasme L.的干燥根,又名斷腸草,始載于《神農(nóng)本草經(jīng)》,瑞香狼毒性味苦平,有逐水祛痰,破疾殺蟲之功效,F(xiàn)代藥理學(xué)和臨床研究表明瑞香狼毒具有抗HIV病毒、抗腫瘤、抗菌、抗結(jié)核、抗白血病、抗驚厥、抗癲癇等作用。目前,對于瑞香狼毒的研究主要集中于某一類或幾種化學(xué)成分的提取、分離,而對其藥材中多組分的同時分析,炮制對各化學(xué)成分的影響及體內(nèi)代謝研究報道較少。本論文根據(jù)目前的研究不足進(jìn)行了以下研究:1、采用MIM-IDA-EPI掃描方式為主,LTQ/Orbitrap mass分析方法為輔的分析方法對瑞香狼毒水提液進(jìn)行分析、鑒定。結(jié)果顯示共鑒定出瑞香狼毒中61種化合物(其中黃酮類23種,香豆素類14種,萜類2種,木脂素6種,苯丙素3種,其它類13種),并對其可能的裂解途徑進(jìn)行推測,總結(jié)質(zhì)譜裂解規(guī)律。該方法簡便、快速,為全面研究瑞香狼毒的化學(xué)組成和質(zhì)量控制奠定了基礎(chǔ),為中藥材的定性鑒別提供有效手段。2、采用正負(fù)離子模式相結(jié)合的MIM-IDA-EPI檢測方式,對炮制前后瑞香狼毒中的特征峰運(yùn)用代謝組學(xué)技術(shù)對瑞香狼毒中的特征峰進(jìn)行比較,采用多元統(tǒng)計法和藥理相結(jié)合的方法對特征峰進(jìn)行篩選、并根據(jù)信息鑒定特征峰。通過分析發(fā)現(xiàn)瑞香狼毒生品和各炮制品間化學(xué)成分具有明顯差異,并發(fā)現(xiàn)炮制后有大量峰存在顯著性差異,其中29個差異變量的結(jié)構(gòu)已得到鑒定。3、建立可同時測定大鼠血漿中新狼毒素A、新狼毒素B、異狼毒素、西瑞香素含量的液質(zhì)聯(lián)用方法,并用于大鼠灌胃給藥瑞香狼毒水提液后該4種成分的藥代動力學(xué)研究。結(jié)果表明血漿中新狼毒素A、B、異狼毒素、西瑞香素在大鼠血漿中的定量下限均可達(dá)0.274 ng/mL,在0.274~200 ng/mL濃度范圍內(nèi)線性關(guān)系良好(r0.99),批內(nèi)和批間精密度(RSD)均小于10%。新狼毒素A在0.5 h(tmax)達(dá)到最大濃度(Cmax)5.24ng/mL,西瑞香素在0.083 h(tmax)達(dá)到最大濃度(Cmax)1.48 ng/mL,表明這兩種物質(zhì)吸收迅速,可快速進(jìn)入血液循環(huán)系統(tǒng)。新狼毒素B和異狼毒素在大鼠血漿中均沒有暴露。
[Abstract]:Stellera chamaejasme is Stellera chamaejasme L. Dry root, also known as amputation grass, first contained in "Shennong Herbal Medicine", daphrophon wolf toxic taste bitter, water dispelling phlegm, killing the efficacy of disease. Modern pharmacological and clinical studies have shown that Daphne chamaejasme has antiviral, antitumor, antimicrobial, antituberculosis, antileukemia, anticonvulsant and antiepileptic effects. At present, the research of chamaeanthus chamaejasme venom is mainly focused on the extraction and separation of one or more chemical constituents, but there are few reports on the effects of processing on each chemical component and metabolism in vivo by simultaneous analysis of multicomponent in its medicinal materials. In this paper, the following research was carried out according to the deficiency of current research: 1. The MIM-IDA-EPI scanning method was used to analyze and identify the aqueous extract of Stellera chamaejasme venom by using the LTQ / Orbitrap mass analysis method. The results showed that 61 compounds (23 flavonoids, 14 coumarins, 2 terpenoids, 6 lignins, 3 phenylpropionins and 13 other species) were identified and their possible cleavage pathways were deduced. The cracking law of mass spectrometry was summarized. The method is simple and rapid, which lays a foundation for the overall study of chemical composition and quality control of Rubus chamaejasme venom, and provides an effective method for the qualitative identification of Chinese medicinal materials. The method of MIM-IDA-EPI combined with positive and negative ion mode is adopted. The characteristic peaks of chamaejus chamaejasme venom before and after processing were compared by metabolic technique. The characteristic peaks were screened by multivariate statistics and pharmacology, and the characteristic peaks were identified according to the information. It was found that there were significant differences in chemical constituents between raw and processed products of chamaejasma chamaejasme and a large number of peaks after processing. The structure of 29 different variables has been identified. A method for simultaneous determination of the contents of neophaliphin A, neopyclotoxin B, isocatoxin, and siderin in plasma of rats was established. The pharmacokinetics of the four components was studied after the rats were given water extract of Daphne chamaejasme. The results showed that the lower limit of plasma quantification of new wolf toxin, isopyclotoxin and ciprofloxacin in plasma of rats was 0.274 ng / mL, the linear relationship was good in the range of 0.274 ~ 200 ng/mL, and the intra and inter-assay precision was less than 10%. The maximum concentration of new wolf toxin A was 5.24ng / mL at 0.5 h / t max, and the maximum concentration of sirosin was 1.48ng / mL at 0.083 h / t _ (max), indicating that the two substances were absorbed rapidly and could enter the blood circulation system quickly. Neither new wolf toxin B nor iso-wolf toxin was exposed to plasma in rats.
【學(xué)位授予單位】:河北大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R284;R285;O657.63
【參考文獻(xiàn)】
相關(guān)期刊論文 前10條
1 高佳;程曉昆;班璐;劉月;祝仕清;;液質(zhì)聯(lián)用技術(shù)的應(yīng)用與發(fā)展[J];當(dāng)代化工研究;2016年05期
2 張雪梅;祖?zhèn)チ?王宣高;師光祿;成軍;;瑞香狼毒根中狼毒色原酮對朱砂葉螨的觸殺毒性[J];北京農(nóng)學(xué)院學(xué)報;2016年02期
3 胡爽;劉峰;陳美言;;不同炮制品瑞香狼毒藥材急性毒性試驗研究[J];安徽農(nóng)業(yè)科學(xué);2015年09期
4 江志峰;馬曉莉;韓波;曹松云;耿媛媛;;不同炮制方法對瑞香狼毒化學(xué)成分的影響[J];醫(yī)學(xué)研究與教育;2015年01期
5 毛多斌;李山;牟定榮;彭國崗;白曉莉;賈春曉;楊靖;;1-L-谷氨酸-1-脫氧-D-果糖的熱裂解分析研究[J];中國煙草學(xué)報;2014年02期
6 徐彬;陳永剛;吳金虎;;中藥復(fù)方藥效物質(zhì)基礎(chǔ)研究的概述[J];醫(yī)學(xué)綜述;2014年01期
7 王星;王永明;田妮娜;;瑞香狼毒炮制前后毒性變化作用的研究[J];科技視界;2013年35期
8 馬曉莉;劉晉芝;曹松云;王淼;張新穎;;酒制瑞香狼毒對荷瘤小鼠抑瘤作用及機(jī)制的實驗研究[J];中成藥;2013年06期
9 陸軍;馬帥;葉松;張雷;段傳軍;陶鈞;李朝品;;中藥狼毒提取物對MDR-TB感染小鼠細(xì)胞免疫的調(diào)節(jié)作用[J];細(xì)胞與分子免疫學(xué)雜志;2012年12期
10 ;In vitro inhibitory and pro-apoptotic effect of Stellera Chamaejasme LExtract on human lung cancer cell line NCI-H157[J];Journal of Traditional Chinese Medicine;2012年03期
相關(guān)博士學(xué)位論文 前3條
1 李s鷏,
本文編號:1949339
本文鏈接:http://sikaile.net/kejilunwen/huaxue/1949339.html