本文關(guān)鍵詞：α-菠菜甾醇對(duì)小鼠小腸P糖蛋白和寡肽轉(zhuǎn)運(yùn)體PepT1藥物轉(zhuǎn)運(yùn)體的影響研究　出處：《四川農(nóng)業(yè)大學(xué)》2016年碩士論文　論文類(lèi)型：學(xué)位論文

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【摘要】：目的：本實(shí)驗(yàn)在中藥引經(jīng)的理論指導(dǎo)下,結(jié)合本實(shí)驗(yàn)室前期對(duì)桔梗引經(jīng)作用的研究方法,首先從桔梗各有效成分中篩選出化學(xué)結(jié)構(gòu)清晰的αα-菠菜甾醇(α-spinasterol)作為研究物質(zhì),然后選用酒石酸泰樂(lè)菌素(Tylosin tartrate)為底藥,利用免疫組化,熒光定量PCR (Realtime fluorescence quantitative PCR, RTFQ PCR)和免疫蛋白印跡(Western blotting, WB)等研究方法,通過(guò)研究α-菠菜甾醇對(duì)小鼠小腸段外排型藥物轉(zhuǎn)運(yùn)體P糖蛋白(P-glycoprotein, P-gp)和攝取型藥物轉(zhuǎn)運(yùn)體寡肽轉(zhuǎn)運(yùn)體1(oligopeptide transporter, PepTl)表達(dá)的影響,初步探討在吸收環(huán)節(jié)上使桔梗發(fā)揮“載藥上行”作用的機(jī)理,為進(jìn)一步研究引經(jīng)作用機(jī)制等實(shí)驗(yàn)提供基礎(chǔ),同時(shí)為驗(yàn)證引經(jīng)理論的科學(xué)性。方法：144只健康昆明小鼠,隨機(jī)分為4個(gè)組,每組36只,雌雄各半。I組：?jiǎn)蝿┝恳淮喂喾?菠菜甾醇[12.5mg/(kg·b·w)];Ⅱ組：?jiǎn)蝿┝恳淮瓮瑫r(shí)灌服α-菠菜甾醇[12.5mg/(kg·b·w)]與酒石酸泰樂(lè)菌素[600mg/(kg·b·w)];Ⅲ組：?jiǎn)蝿┝恳淮喂喾剖崽?lè)菌素[600mg/(kg·b·w)];Ⅳ組：?jiǎn)蝿┝恳淮喂喾睇}水。每組按0.2mL·10g-1BW的劑量共灌胃5天,分別在1,3,5天后處死一批采樣。采用免疫組化,熒光定量PCR和免疫蛋白印跡的方法測(cè)定1,3,5天的小鼠腸道上P-gp和PepTl的表達(dá)的變化。結(jié)果：從三個(gè)方法的結(jié)果來(lái)看：I組(a-菠菜甾醇組)和II組(混合組)相對(duì)于Ⅳ組(對(duì)照組)外排型藥物轉(zhuǎn)運(yùn)體P-gp表達(dá)減少或強(qiáng)度減弱：而攝取型藥物轉(zhuǎn)運(yùn)體PepT1表達(dá)增多或強(qiáng)度增強(qiáng);而III組(酒石酸泰樂(lè)菌素組)的外排型藥物轉(zhuǎn)運(yùn)體P-gp表達(dá)增多或強(qiáng)度增強(qiáng)：攝取型藥物轉(zhuǎn)運(yùn)體PepT1表達(dá)減少或強(qiáng)度減弱,且都隨著用藥時(shí)間的延長(zhǎng)差異性越來(lái)越顯著(P0.01)。其中免疫組化結(jié)果表明,P-gp在十二指腸的變化差異較空腸和回腸更加明顯,而PepT1在空腸的變化比十二指腸和回腸更為顯著；熒光定量PCR和免疫印跡結(jié)果顯示,P-gp在各腸段的表達(dá)是從近端到遠(yuǎn)端逐漸遞增,而PepTl在各腸段的表達(dá)在十二指腸最多,在空腸和回腸依次遞減。結(jié)論：①α-菠菜甾醇具有抑制藥物轉(zhuǎn)運(yùn)體P-gp表達(dá)和促進(jìn)藥物轉(zhuǎn)運(yùn)體PepT1表達(dá)的作用。②酒石酸泰樂(lè)菌素具有促進(jìn)P-gp表達(dá)和抑制PepTl表達(dá)的作用。③桔梗“引經(jīng)”在吸收環(huán)節(jié)上的作用機(jī)理之一是作用于腸道上的藥物轉(zhuǎn)運(yùn)體。④酒石酸泰樂(lè)菌素和α-菠菜甾醇產(chǎn)生的藥物間相互作用(Drug-drug interaction, DDI)的機(jī)制之一是通過(guò)作用于P-gp和PepT1兩個(gè)靶點(diǎn)。
[Abstract]:Objective: this experiment through theory in traditional Chinese medicine, combined with the previous research methods of Platycodon grandiflorum cited by the role, first screened clear chemical structure of alpha spinasterol from the active ingredient of Platycodon grandiflorum (alpha -spinasterol) as the research material, and then choose a wine stone acid tylosin (Tylosin tartrate) for the end of medicine, by immunohistochemistry, fluorescence quantitative PCR (Realtime fluorescence quantitative PCR, RTFQ PCR) and Western blot (Western blotting, WB) and other research methods, through the study of alpha spinasterol on mice intestinal drug efflux transporter P glycoprotein (P-glycoprotein, P-gp) and drug uptake transporter peptide transporter 1 (oligopeptide transporter, PepTl) on the expression of the preliminary discussion on the absorption of links to play "loading up mechanism of Platycodon", for further study cited by the mechanism of real 楠屾彁渚涘熀紜，

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