本文選題：羧酸酯酶1　切入點(diǎn)：肝損傷　出處：《大連醫(yī)科大學(xué)》2017年碩士論文

【摘要】：哺乳動(dòng)物的羧酸酯酶(CEs)是重要的絲氨酸水解酶家族的成員,Ces可以分為5個(gè)亞型,但最主要的亞型是羧酸酯酶1(CE1)和羧酸酯酶2(CE2),主要存在于組織的內(nèi)質(zhì)網(wǎng)腔內(nèi)。人類羧酸酯酶1(Human Carboxylesterases 1,hCE1)作為一類代謝酶,廣泛存在于人體肝臟、腎臟及皮膚等組織中,但卻在肝臟中特異性分布且含量極高。hCE1負(fù)責(zé)水解各種內(nèi)源性物質(zhì)包括膽固醇酯,甘油三酯等,并在維持機(jī)體脂質(zhì)代謝平衡中起著關(guān)鍵的作用。此外還催化水解各種外源性物質(zhì),如某些臨床藥物和環(huán)境毒素,在機(jī)體的防御體系中也扮演重要角色。由于hCE1在肝臟中特異性分布,當(dāng)肝臟收到損傷時(shí),肝細(xì)胞破裂后釋放入血,在血中可以檢測到該酶。肝臟為人體極為重要的臟器之一,是體內(nèi)各種碳水化合物、蛋白質(zhì)、脂質(zhì)、維生素合成代謝的主要器官,并且在分泌、排泄、解毒、生物轉(zhuǎn)化等方面也發(fā)揮著重要作用�；诟翁厥獾慕馄饰恢眉捌渖砉δ�,多種內(nèi)源性或外源性的因素,比如:病毒、細(xì)菌、炎癥因子、藥物、環(huán)境毒物等都能引起肝功能不同程度受損,最終導(dǎo)致疾病發(fā)生。肝損傷的準(zhǔn)確預(yù)測和診斷是臨床醫(yī)學(xué)的研究熱點(diǎn),受到研究者的廣泛關(guān)注。由于損傷的機(jī)制較為復(fù)雜,影響因素多,常常涉及到諸多代謝反映的參與,或是引起免疫反應(yīng),因此其檢查方法依然存在很多問題。較好的血清標(biāo)志物需要具有快速,簡便,靈敏準(zhǔn)確且早期就能反應(yīng)出問題所在。目前臨床上對(duì)肝損傷主要是進(jìn)行肝生化檢查,包括一些肝臟酶學(xué)檢查,肝合成功能及肝纖維化血清學(xué)指標(biāo)等,能較全面的反映肝功能。其中肝纖維化指標(biāo)較為特異,但不夠敏感�？紤]到這些指標(biāo)不能有效進(jìn)行分類,不能較早的反映肝功能,需要結(jié)合其他的相關(guān)指標(biāo)進(jìn)行綜合考慮。隨著近年來蛋白組學(xué)、代謝組學(xué)和臨床檢驗(yàn)相關(guān)學(xué)科和技術(shù)的快速發(fā)展,越來越多的新型血清學(xué)指標(biāo)將被發(fā)現(xiàn),彌補(bǔ)了傳統(tǒng)指標(biāo)的一些不足,但是大部分尚停留在研究階段。因此,發(fā)現(xiàn)并驗(yàn)證新型血清標(biāo)志物對(duì)于肝損傷的早期診斷與治療具有重要意義。本文采用羧酸酯酶1的特異性小分子熒光探針對(duì)血漿中hCE1的進(jìn)行檢測,該探針為hCE1的底物,被hCE1代謝后產(chǎn)生相應(yīng)的產(chǎn)物,通過高效液相色譜熒光分析,根據(jù)產(chǎn)物的生成量,以測定羧酸酯酶的活性。用此方法檢測不同原因造成的肝損傷血清中的hCE1的活性,以此來分析探求該酶與不同肝臟疾病的關(guān)系,并與目前臨床比較認(rèn)可的肝損傷標(biāo)準(zhǔn)進(jìn)行相關(guān)性分析,探究其作為新型標(biāo)志物的可行性及意義。
[Abstract]:Ces, a member of the important serine hydrolase family, can be divided into five subtypes, but the main subtypes are carboxylesterase 1 (CE1) and carboxylesterase 2 (CE2), which mainly exist in the endoplasmic reticulum (ER) cavity of tissues.Human carboxylesterase 1(Human Carboxylesterases 1hCE1 is a kind of metabolic enzyme, which widely exists in human liver, kidney, skin and other tissues. However, it is specifically distributed in the liver and contains a high content of HCE1, which is responsible for the hydrolysis of various endogenous substances, including cholesterol ester.Triglyceride plays a key role in maintaining the balance of lipid metabolism.In addition, the catalytic hydrolysis of various exogenous substances, such as some clinical drugs and environmental toxins, also plays an important role in the body's defense system.Because of the specific distribution of hCE1 in the liver, when the liver is damaged, the liver cells release into the blood after rupture, and the enzyme can be detected in the blood.As one of the most important organs in human body, liver is the main organ of carbohydrate, protein, lipid, vitamin synthesis and metabolism, and also plays an important role in secretion, excretion, detoxification, biotransformation and so on.Based on the special anatomical location and physiological function of the liver, many endogenous and exogenous factors, such as virus, bacteria, inflammatory factors, drugs and environmental poisons, can damage liver function to varying degrees and eventually lead to disease.The accurate prediction and diagnosis of liver injury is a hot topic in clinical medicine.Because the mechanism of injury is more complex and there are many factors affecting it, it often involves many metabolic reactions, or causes immune response, so there are still many problems in its examination method.Better serum markers need to be quick, simple, sensitive, accurate and early to respond to the problem.At present, liver injury is mainly examined by biochemical examination of liver, including some liver enzyme examination, liver synthesis function and liver fibrosis serological index, which can reflect liver function comprehensively.The indexes of liver fibrosis were specific, but not sensitive.Considering that these indexes can not be classified effectively and can not reflect liver function earlier, it needs to be considered synthetically with other related indexes.With the rapid development of proteomics, metabolomics and clinical laboratory related disciplines and techniques, more and more new serological indicators will be found, which make up for some shortcomings of traditional indicators, but most of them are still in the research stage.Therefore, it is important to find and verify new serum markers for early diagnosis and treatment of liver injury.In this paper, hCE1 in plasma was detected by using a specific small molecular fluorescence probe of carboxylesterase 1. The probe was the substrate of hCE1, which was metabolized by hCE1 to produce corresponding products. The products were analyzed by high performance liquid chromatography (HPLC).To determine the activity of carboxylate esterase.This method was used to detect the activity of hCE1 in the serum of liver injury caused by different causes, so as to analyze the relationship between the enzyme and different liver diseases, and to analyze the correlation between the enzyme and the current approved liver injury standard.Explore its feasibility and significance as a new type of marker.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R575

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本文編號(hào)：1707056