本文關(guān)鍵詞： 原位腦灌流技術(shù) 血腦屏障 轉(zhuǎn)運動力學(xué) 肼 一甲基肼 噻諾啡　出處：《中國人民解放軍軍事醫(yī)學(xué)科學(xué)院》2005年碩士論文　論文類型：學(xué)位論文

【摘要】：原位腦灌流技術(shù)是研究物質(zhì)跨BBB轉(zhuǎn)運機(jī)制的一種快速、敏感、定量、可控的方法,在藥物或毒物動力學(xué)上有廣泛的應(yīng)用。它可簡便地描繪出物質(zhì)入腦的動力學(xué)變化,結(jié)合血管清除方法可以區(qū)分真正的跨膜轉(zhuǎn)運入腦和單純的內(nèi)皮細(xì)胞積聚,可研究物質(zhì)的跨BBB轉(zhuǎn)運機(jī)制。本研究應(yīng)用大鼠原位腦灌流技術(shù),結(jié)合血管清除方法和多點吸收數(shù)據(jù)分析,建立了外源化合物跨BBB轉(zhuǎn)運的動力學(xué)模型。大鼠原位腦灌流系統(tǒng)主要由液體輸送系統(tǒng)及其附屬設(shè)備組成,各部分均經(jīng)過嚴(yán)格的挑選與調(diào)試;并在硬件構(gòu)建完成后對該技術(shù)的操作和各種條件進(jìn)行了優(yōu)化。經(jīng)實驗驗證原位腦灌流是表達(dá)血腦轉(zhuǎn)運特征的一種可靠技術(shù),其操作比較簡便,具有活體的真實性,且方法可靠,條件可控,結(jié)果穩(wěn)定。血管清除實驗可以有效區(qū)分真正入腦實質(zhì)的轉(zhuǎn)運和血管組織的內(nèi)吞與簡單結(jié)合。多點吸收數(shù)據(jù)分析方法能夠表征外源化合物進(jìn)入腦組織的動力學(xué)特征。 重新確證了肼和MMH在腦組織樣品中的對-二甲氨基苯甲醛(p-DMBA)比色測定方法;新建立了噻諾啡的以液-液萃取為生物樣品前處理的HPLC-UV定量分析方法,并從特異性、靈敏度、線性范圍、精密度、準(zhǔn)確度以及樣品的穩(wěn)定性進(jìn)行了方法學(xué)的確證。這三種化合物在腦組織樣品中的測定方法均符合動力學(xué)實驗要求,能夠滿足各自跨BBB轉(zhuǎn)運動力學(xué)研究的需要。 采用大鼠原位腦灌流方法,結(jié)合血管清除方法以及多點吸收分析的動力學(xué)模型研究了肼、MMH和噻諾啡三種外源化合物跨BBB轉(zhuǎn)運的動力學(xué)特征,結(jié)果顯示三者均可跨過BBB進(jìn)入腦實質(zhì),入腦濃度隨著灌流濃度和灌流時間的增加而呈上升趨勢;三者在各自灌流濃度下跨BBB轉(zhuǎn)運的速度常數(shù)K_(in)依次為0.01、0.02和
[Abstract]:In situ cerebral perfusion is a rapid, sensitive, quantitative and controllable method to study the transport mechanism of substance across BBB. It is widely used in the pharmacokinetics of drugs or poisons. It can easily describe the dynamic changes of substance into the brain and can distinguish the true transmembrane transport into the brain and the accumulation of endothelial cells in combination with vascular clearance. In this study, we used in situ brain perfusion technique, combined with vascular clearance method and multi-point absorption data analysis. A kinetic model for the transport of exogenous compounds across BBB was established. The in-situ cerebral perfusion system in rats was mainly composed of liquid delivery system and its auxiliary equipment. All parts were selected and adjusted strictly. After the completion of the hardware construction, the operation and various conditions of the technique were optimized. It is proved by experiments that in situ brain perfusion is a reliable technique to express the characteristics of blood brain transport, and its operation is relatively simple. The method is reliable and the condition is controllable. The results are stable. Vascular clearance experiments can effectively distinguish the transport into brain parenchyma and the endocytosis and simple combination of vascular tissue. Multi-point absorption data analysis method can characterize the dynamic characteristics of exogenous compounds entering brain tissue. . The colorimetric method of p-dimethylaminobenzaldehyde (p-DMBA) for determination of hydrazine and MMH in brain tissue samples was reconfirmed. A new HPLC-UV method for quantitative analysis of tienorphine with liquid-liquid extraction as biological sample was established, and the specificity, sensitivity, linear range and precision were analyzed. The accuracy and stability of the samples were confirmed by the methodology. The determination of these three compounds in brain tissue samples met the requirements of kinetic experiments. It can meet the needs of the study on the transport kinetics of BBB. The kinetic characteristics of the transport of three exogenous compounds of hydrazine and tienorphine through BBB were studied by in situ cerebral perfusion in rats combined with vascular clearance and multipoint absorption analysis. The results showed that all three crossed BBB into brain parenchyma, and the brain concentration increased with the increase of perfusion concentration and perfusion time. The velocity constant of BBB transport among the three groups under their respective irrigation concentration is 0.01g / 0.02 and 0.01 / 0. 02, respectively.
【學(xué)位授予單位】：中國人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2005
【分類號】：R363

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