本文選題：咖啡酸對硝基苯乙酯 + 血小板　； 參考：《西南大學(xué)》2014年碩士論文

【摘要】：咖啡酸苯乙酯來源于蜂膠,是其主要活性成分之一,文獻(xiàn)報(bào)道它具有多種生物活性,例如抗病毒、抗菌、抗氧化、免疫調(diào)節(jié)、抗腫瘤、心肌缺血再灌注損傷保護(hù)等生理活性,它在民間的用藥史很悠久,主要用于中東地區(qū),在民間蜂膠是一種常用的養(yǎng)生保肝的天然產(chǎn)物；咖啡酸苯乙酯的分子結(jié)構(gòu)為O-二羥基苯基結(jié)構(gòu)和兩個鄰位的酚羥基,前面的基團(tuán)是清除自由基的活性基團(tuán),而后者是容易被氧化的。本文研究了咖啡酸苯乙酯的衍生物,考察其在抗血小聚集方面的活性及其可能的機(jī)制和藥動學(xué)研究。 本文研究了咖啡酸對硝基苯乙酯抑制體外大鼠的血小板聚集的活性,分別比較了空白對照組、陽性對照組(咖啡酸苯乙酯)、實(shí)驗(yàn)組的(咖啡酸對硝基苯乙酯)抗血小板聚集的活性,研究了他們對膠原激活的血小板的生理代謝過程的影響,如血小板聚集率的改變,為進(jìn)一步闡述咖啡酸對硝基苯乙酯抑制膠原誘導(dǎo)的血小板聚集的機(jī)制,本文考察了其對血小板處理后,血小板內(nèi)的一氧化氮的釋放、環(huán)磷酸鳥苷(cGMP)變化、血栓素A2(TXA2)的形成、環(huán)氧合酶-1(COX-1)的活性、5-羥色胺(5-HT)的分泌釋放情況。這些物質(zhì)的變化都與血小板的激活、信號的傳導(dǎo)、代謝有著密切的聯(lián)系。 體外的實(shí)驗(yàn)證明,咖啡酸對硝基苯乙酯和咖啡酸苯乙酯均能夠抑制膠原(Collagen)誘導(dǎo)的大鼠洗滌血小板和PRP血漿的血小板的聚集,咖啡酸對硝基苯乙酯(CAPE-NO2)在1.5-12μM對血小板的聚集抑制呈現(xiàn)劑量依賴性,抑制了血小板的聚集率分別為62%、52%、46%、34%,與空白組相比在咖啡酸對硝基苯乙酯12gM時對血小板的聚集抑制率為55%,而咖啡酸苯乙酯(1.5μM)對血小板的聚集抑制率是14%,因此咖啡酸苯乙酯和咖啡酸對硝基苯乙酯對血小板有很好的抑制聚集活性。血小板中的NO水平顯著的被咖啡酸對硝基苯乙酯和咖啡酸苯乙酯升高,CAPE-NO2對血小板中的NO的作用呈劑量依賴性；咖啡酸對硝基苯乙酯顯著的增加了細(xì)胞的cGMP的含量,與劑量成正比關(guān)系。咖啡酸對硝基苯乙酯在濃度為1.5、3、6、12μM時抑制了血栓素B2的產(chǎn)生分別是9.5%、23%、40%、51%,但是咖啡酸苯乙酯在1.5μM時的抑制率為18%�？Х人釋ο趸揭阴ピ跐舛�1.5-12gM時抑制環(huán)氧合酶-1的活性；在不同濃度(1.5、3、6、12μM)下的5-HT的釋放量為454μg/L、435μg/L、408μg/L、376μg/L,咖啡酸對硝基苯乙酯在12μM時對5-HT的抑制率為87%,而1.5μM的咖啡酸苯乙酯為19%。它的抑制作用的有可能涉及了以下的機(jī)制：咖啡酸對硝基苯乙酯激活了NO/cGMP的信號通路,分別增加了NO的釋放過程和cGMP的產(chǎn)生,咖啡酸對硝基苯乙酯也抑制了環(huán)氧合酶-1的活性,導(dǎo)致血栓素B2的減少；最后咖啡酸對硝基苯乙酯減少了5-羥色胺從激活的血小板的分泌。 通過采用HPLC-UV建立了咖啡酸對硝基苯乙酯肌肉注射大鼠血漿中的含量測定方法,并進(jìn)行藥代動力學(xué)研究。色譜柱為SepaxHP-C18(4.6mm x250mm,5μm),流動相為乙腈-水(55：45),檢測波長329nm,流速為1mL·min-1,柱溫30℃,進(jìn)樣量20μL,血液中咖啡酸對硝基苯乙酯的濃度在50-2000ng.mL-1范圍內(nèi)線性關(guān)系良好,相關(guān)系數(shù)r=0.9999,定量下限為0.05μg·mL-1。用DAS3.0軟件分析后,咖啡酸對硝基苯乙酯在SD大鼠體內(nèi)的藥物代謝動力學(xué)符合二室開放模型,Cmax為976.66μg·L-1, tmax為1h,tl/2α為0.95h,t1/2β為5.51h, AUC0-t為2649.77μg·h·L-1, AUC0-∞為2837.77μg·h·L-1.
[Abstract]:Caffeic acid benzoate is one of the main active ingredients of propolis. It is reported that it has many biological activities, such as antiviral, antibacterial, antioxidation, immunomodulating, anti tumor, protection of myocardial ischemia reperfusion injury and so on. It has a long history in the folk medicine, mainly used in the Middle East, and is a common use in folk propolis. The natural product of health preserving liver preservation; the molecular structure of caffeic acid benzoethyl ester is O- two hydroxy phenyl structure and two ortho phenolic hydroxyl groups. The front group is the active group for scavenging free radicals, and the latter is easily oxidized. The mechanism of energy and the study of pharmacokinetics.
This paper studied the activity of caffeic acid on the inhibition of platelet aggregation in rats with nitrobenzene, compared with the blank control group, the positive control group (caffeic acid benzol), the activity of the antiplatelet aggregation in the experimental group (caffeic acid to nitrobenzene ethyl), and the effect of their effects on the physiological metabolism of the platelets activated by collagen. In order to further elaborate the mechanism of platelet aggregation induced by caffeic acid against nitrobenzene, the release of nitric oxide in platelets, the changes in cGMP, the formation of thromboxane A2 (TXA2), the activity of cyclooxygenase -1 (COX-1), 5- hydroxytryptamine (5-), and 5- hydroxytryptamine (5-) were investigated. The secretion and release of HT. These changes are closely related to platelet activation, signal transduction and metabolism.
In vitro experiments showed that caffeic acid against nitrobenzene and caffeic acid benzoethyl could inhibit the aggregation of platelet in rat washed platelets and PRP plasma induced by collagen (Collagen). The inhibition of platelet aggregation by caffeic acid to nitrobenzene (CAPE-NO2) was dose-dependent on the inhibition of platelet aggregation in 1.5-12 mu M, inhibiting the aggregation rate of platelets respectively 62%, 52%, 46%, 34%, compared with the blank group, the inhibition rate of platelet aggregation was 55% on the caffeic acid to nitrobenzene ethyl 12gM, while the inhibition rate of caffeic acid benzoate (1.5 mu M) on platelet aggregation was 14%. Therefore, caffeic acid benzoethyl and caffeic acid had a good inhibitory aggregation activity on the platelets. The NO level in platelets The effect of caffeic acid on nitrobenzene and caffeic acid benzoate was significantly increased, and the effect of CAPE-NO2 on the NO in platelets was dose-dependent; caffeic acid to nitrobenzene significantly increased the cGMP content of the cell, and was proportional to the dose. Caffeic acid against nitrobenzene at the concentration of 1.5,3,6,12 u M inhibited the production of thromboxane B2. The results were 9.5%, 23%, 40%, 51% respectively, but the inhibition rate of caffeic acid benzol at 1.5 um M was 18%. caffeic acid to nitrobenzene at the concentration of 1.5-12gM, the activity of cyclooxygenase -1 was inhibited. The release of 5-HT at different concentrations (1.5,3,6,12 mu M) was 454 mu, 435, 408, 408 mu, 376 mu g/L, and caffeic acid to nitrobenzene was in 12 mu M. The inhibitory rate was 87%, while the inhibitory action of 1.5 M caffeic acid benzol to 19%. may involve the following mechanism: caffeic acid activates the NO/cGMP signaling pathway to nitrobenzene, which increases the release process of NO and the production of cGMP, and the caffeic acid against nitrobenzene also inhibits the activity of cyclooxygenase -1, leading to thromboxane. The reduction of B2; finally, caffeic acid on NP reduced the secretion of 5- HT from activated platelets.
The content determination method of caffeic acid to nitrobenzene was established by HPLC-UV, and the pharmacokinetics was studied. The chromatographic column was SepaxHP-C18 (4.6mm x250mm, 5 mu m), the mobile phase was acetonitrile water (55:45), the detection wavelength 329nm, the velocity of 1mL. Min-1, the column temperature of 30, 20 mu L, and the caffeic acid to nitrate in the blood. The relationship between the concentration of ethyl benzene ethyl ester in the range of 50-2000ng.mL-1 is good, the correlation coefficient is r=0.9999, the quantitative lower limit is 0.05 mu g. ML-1. is analyzed by DAS3.0 software. The pharmacokinetics of caffeic acid to nitrobenzene ethyl ester in SD rats conforms to the two chamber open model, Cmax is 976.66 Mu G. L-1, Tmax is 1H, tl/2 alpha is UC0-t is 2649.77 g h L-1 and AUC0- infinity is 2837.77 g g h L-1..

【學(xué)位授予單位】：西南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R96

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