【摘要】：背景與目的:咖啡酸苯乙酯（CAPE）是蜂膠中的一種主要活性組分，屬于多酚類化合物，是一種強(qiáng)抗氧化劑，有清除自由基的功效。在抗腫瘤、抗氧化、抗炎癥、免疫調(diào)節(jié)、缺血-再灌注保護(hù)等方面表現(xiàn)出獨(dú)特的生理藥理作用。許多報(bào)告及文獻(xiàn)已經(jīng)證實(shí)，CAPE藥理活性與鄰二酚羥基的存在有關(guān)。通過(guò)對(duì)CAPE進(jìn)行修飾，得到咖啡酸苯乙酯的一種衍生物，即對(duì)硝基咖啡酸苯乙酯（CAPE-NO2）。因其也具有CAPE的必需活性基團(tuán)，因此我們推測(cè)咖啡酸苯乙酯衍生物-對(duì)硝基咖啡酸苯乙酯也應(yīng)具有CAPE相關(guān)的一些藥理活性。 本研究采用腹腔注射CCl4制備小鼠肝損傷模型，然后給予對(duì)硝基咖啡酸苯乙酯，觀察其對(duì)小鼠肝損傷模型的肝臟保護(hù)作用，并對(duì)其作用機(jī)制進(jìn)行初步探討。旨在為CCl4引起的化學(xué)性肝損傷尋找一種新的治療物質(zhì)。 方法：昆明小鼠隨機(jī)分為5組，每組10只。正常對(duì)照組：腹腔注射生理鹽水0.1ml/10g；模型對(duì)照組：腹腔注射生理鹽水0.1ml/10g；對(duì)硝基咖啡酸苯乙酯高、中、低劑量實(shí)驗(yàn)組分別腹腔注射對(duì)硝基咖啡酸苯乙酯2.0mg/kg，1.0mg/kg，0.5mg/kg。連續(xù)15天后，正常組腹腔注射橄欖油溶液（0.1ml/10g），其余各組腹腔注射0.15％CCl4橄欖油溶液（0.1ml/10g）。禁食24h后眼眶采血，離心分離血清測(cè)定AST、ALT水平；處死小鼠，取肝臟稱重，計(jì)算肝臟指數(shù)；取肝右葉制備10%肝勻漿，測(cè)定MDA、SOD、GSH-Px及其CAT活性。取肝左葉經(jīng)10%多聚甲醛固定，進(jìn)行組織病理學(xué)檢查。 結(jié)果：（1）與模型組相比，CAPE-NO2各組均能明顯降低小鼠血清中AST、ALT的活性（P0.05），其降低程度呈劑量依賴性；（2）與模型組相比，，CAPE-NO2各組均能明顯降低小鼠肝組織中MDA的含量（P0.05），其降低程度呈劑量依賴性；（3）與模型組相比，CAPE-NO2各組均能明顯升高小鼠肝組織中SOD、CAT、GSH-Px的活性（P0.05），其升高程度呈劑量依賴性；（4）與模型組相比，CAPE-NO2各劑量組可顯著降低小鼠肝臟指數(shù)（P0.05）；（5）與模型組相比，CAPE-NO2各劑量組肝細(xì)胞變性、壞死有不同程度的減輕，其中CAPE-NO2大劑量組肝細(xì)胞損傷相對(duì)較輕，以水變性為主，偶見(jiàn)壞死；（6）CAPE-NO2高、中劑量組小鼠肝細(xì)胞凋亡率與模型組相比明顯下降，差異有統(tǒng)計(jì)學(xué)意義（P0.01）。 結(jié)論：CAPE-NO2對(duì)小鼠化學(xué)性肝損傷具有保護(hù)作用，機(jī)制可能與其保護(hù)肝細(xì)胞膜、清除自由基、減輕脂質(zhì)過(guò)氧化和抑制細(xì)胞凋亡有關(guān)。但其具體機(jī)制有待進(jìn)一步深入研究。
[Abstract]:Background & AIM: phenylethyl coffee acid (CAPE) is a main active component in propolis. It belongs to polyphenols and is a strong antioxidant, which has the effect of scavenging free radicals. It has unique physiological and pharmacological effects in anti-tumor, antioxidation, anti-inflammation, immunomodulation, ischemia-reperfusion protection and so on. Many reports and literatures have confirmed that the pharmacological activity of CAPE is related to the existence of o-diphenol hydroxyl groups. Phenylethyl p-nitrocoffee (CAPE-NO2), a derivative of phenylethyl coffee acid, was obtained by modifying CAPE. Because it also has the necessary active groups of CAPE, we speculate that phenylethyl p-nitrocoffee should also have some pharmacological activities related to CAPE. In this study, the mouse model of liver injury was established by intraabdominal injection of CCl4, and then phenylethyl p-nitrocoffee was given to observe the protective effect of phenylethyl nitrocoffee on the model of liver injury in mice, and the mechanism of action was discussed. The purpose of this study was to find a new therapeutic substance for chemical liver injury induced by CCl4. Methods: Kunming mice were randomly divided into 5 groups with 10 mice in each group. Normal control group: saline 0.1 ml 鈮

本文編號(hào)：2501148