本文選題：Omentin-1 + 丹參酮IIA��； 參考：《南華大學(xué)》2016年博士論文

【摘要】：動(dòng)脈粥樣硬化(Atherosclerosis,As)在全球的罹患率以及致死率都名居前列,嚴(yán)重危害人類的健康。在動(dòng)脈粥樣硬化早期,其標(biāo)志性病理特征是血管內(nèi)皮下大量的巨噬細(xì)胞內(nèi)脂質(zhì)蓄積以及泡沫細(xì)胞的形成。泡沫細(xì)胞最終壞死崩解,釋放出細(xì)胞內(nèi)的膽固醇,是構(gòu)成動(dòng)脈粥樣硬化斑塊的最主要成分,促進(jìn)動(dòng)脈粥樣硬化的進(jìn)一步進(jìn)展。因此,促進(jìn)巨噬細(xì)胞內(nèi)膽固醇流出及體內(nèi)膽固醇逆向轉(zhuǎn)運(yùn)(reverse cholesterol transport,RCT),從而抑制泡沫細(xì)胞形成和血管壁內(nèi)脂質(zhì)沉積,對(duì)動(dòng)脈粥樣硬化性的防治具有重要意義。三磷酸腺苷結(jié)合盒轉(zhuǎn)運(yùn)體A1(ATP binding cassette transporter A1,ABCA1)是一個(gè)膜整合蛋白,其以ATP作為能源將胞內(nèi)游離的膽固醇及磷脂轉(zhuǎn)運(yùn)至胞膜的外側(cè)面,最終與貼附在細(xì)胞表面的載脂蛋白AI(apoprotein AI,apoAI)結(jié)合,從而形成新生的高密度脂蛋白(high density lipoprotein,HDL)。這是HDL生成所必需的過(guò)程,也是促進(jìn)巨噬細(xì)胞內(nèi)過(guò)多的膽固醇外流以及rct的關(guān)鍵步驟。abca1在巨噬細(xì)胞中的表達(dá)以及其活性往往受到轉(zhuǎn)錄及轉(zhuǎn)錄后水平的精細(xì)調(diào)控。網(wǎng)膜素(omentin)是一類新發(fā)現(xiàn)的脂肪細(xì)胞因子,主要由網(wǎng)膜脂肪組織表達(dá)和釋放。值得注意的是,研究發(fā)現(xiàn)這種基因可調(diào)節(jié)葡萄糖攝取。肥胖或肥胖相關(guān)疾病患者,包括2型糖尿病、內(nèi)皮功能障礙、頸動(dòng)脈粥樣硬化和冠狀動(dòng)脈疾病,發(fā)現(xiàn)其血漿omentin-1水平降低了。研究證明,omentin-1與高密度脂蛋白膽固醇(hdl-c)呈正相關(guān),與葡萄糖和甘油三酸酯水平呈負(fù)相關(guān)。代謝綜合征(mets)初期患者循環(huán)omentin-1水平異常者其罹患糖尿病和心血管疾病的風(fēng)險(xiǎn)更高。因此,omentin-1與代謝綜合征密切相關(guān),在代謝綜合征患者的動(dòng)脈粥樣硬化發(fā)生發(fā)展中產(chǎn)生重要作用。omentin-1在rct、脂質(zhì)代謝和as中差異表達(dá)的發(fā)現(xiàn)為我們提供了新的途徑和視角。因此,omentin-1有望成為心血管保護(hù)因子和干預(yù)靶點(diǎn)之一。然而,omentin-1在abca1表達(dá)及導(dǎo)致提高h(yuǎn)dl功能和膽固醇逆向轉(zhuǎn)運(yùn)中的作用研究尚少。本研究中,我們研究omentin-1對(duì)巨噬細(xì)胞abca1表達(dá)的作用和潛在的分子機(jī)制。為了探討omentin-1抗動(dòng)脈粥樣硬化的相關(guān)作用機(jī)制,我們首先在第一部分實(shí)驗(yàn)中觀察omentin-1對(duì)thp-1巨噬細(xì)胞abca1表達(dá)、胞內(nèi)膽固醇流出和脂質(zhì)含量的影響。在第二部分實(shí)驗(yàn)中我們探索了omentin-1介導(dǎo)thp-1巨噬細(xì)胞abca1表達(dá)及膽固醇流出的作用機(jī)制。接著,我們?cè)诘谌糠謱?shí)驗(yàn)中,觀察了omentin-1對(duì)apoe-/-小鼠的血脂水平、膽固醇逆向轉(zhuǎn)運(yùn)和動(dòng)脈粥樣硬化病變的影響。最后,我們?cè)诘谒牟糠謱?shí)驗(yàn)中,觀察了具有較強(qiáng)調(diào)脂作用的丹參酮iia(tanshinoneiia,tan)對(duì)巨噬細(xì)胞的omentin-1和abca1的表達(dá)、脂質(zhì)代謝,以及對(duì)apoe-/-小鼠的動(dòng)脈粥樣硬化病變的影響,研究tan通過(guò)上調(diào)omentin-1發(fā)揮抗動(dòng)脈粥樣硬化的作用機(jī)制。本研究揭示了omentin-1抗動(dòng)脈粥樣硬化的作用以及機(jī)制,也許為動(dòng)脈粥樣硬化性疾病提供新的防治靶點(diǎn)。第1章omentin-1對(duì)thp-1巨噬細(xì)胞abca1表達(dá)及膽固醇流出的影響目的:觀察omentin-1對(duì)thp-1巨噬細(xì)胞abca1mrna及蛋白表達(dá)水平、胞內(nèi)膽固醇流出和脂質(zhì)含量的影響。方法:用omentin-1和/或lxrαsirna處理thp-1源性巨噬細(xì)胞后,用rt-pcr方法檢測(cè)各個(gè)實(shí)驗(yàn)組細(xì)胞的abca1mrna的表達(dá),westernblot檢測(cè)abca1蛋白水平,hplc檢測(cè)胞內(nèi)總膽固醇(tc)游離膽固醇(fc)及膽固醇酯(ce)含量,液體閃爍計(jì)數(shù)儀檢測(cè)胞內(nèi)膽固醇流出,油紅o染色觀察胞內(nèi)脂滴情況。結(jié)果:omentin-1呈時(shí)間和濃度依賴性上調(diào)巨噬細(xì)胞abca1的表達(dá),促進(jìn)胞內(nèi)膽固醇流出,降低胞內(nèi)tc、fc和ce含量,抑制胞內(nèi)脂質(zhì)蓄積和泡沫細(xì)胞形成。而abca1sirna與omentin-1共處理細(xì)胞后,明顯抑制omentin-1促膽固醇流出的作用,胞內(nèi)脂質(zhì)蓄積和泡沫細(xì)胞形成明顯加劇。結(jié)論:(1)omentin-1增加thp-1巨噬細(xì)胞abca1mrna和蛋白表達(dá)。(2)omentin-1促進(jìn)abca1介導(dǎo)的thp-1巨噬細(xì)胞脂質(zhì)流出,抑制巨噬細(xì)胞內(nèi)脂質(zhì)蓄積和泡沫細(xì)胞形成。第2章omentin-1介導(dǎo)thp-1巨噬細(xì)胞abca1表達(dá)及膽固醇流出的作用機(jī)制目的:探索omentin-1介導(dǎo)thp-1巨噬細(xì)胞abca1表達(dá)及膽固醇流出的作用機(jī)制。方法:分別用omentin-1或和lxrαsirna、pi3ksirna、aktsirna、pi3k抑制劑ly2940029及akt抑制劑himo處理thp-1源性巨噬細(xì)胞24h后,westernblot檢測(cè)abca1lxrα蛋白水平,hplc檢測(cè)胞內(nèi)總膽固醇(tc)游離膽固醇(fc)及膽固醇酯(ce)含量,液體閃爍計(jì)數(shù)儀檢測(cè)胞內(nèi)膽固醇流出,油紅o染色觀察胞內(nèi)脂滴情況。結(jié)果:omentin-1上調(diào)巨噬細(xì)胞abca1的表達(dá),促進(jìn)胞內(nèi)膽固醇流出,降低胞內(nèi)tc、fc和ce含量,抑制胞內(nèi)脂質(zhì)蓄積和泡沫細(xì)胞形成。而分別加用lxrαsirna、pi3ksirna、aktsirna、pi3k抑制劑ly2940029及akt抑制劑himo與omentin-1共處理細(xì)胞后,明顯抑制abca1的表達(dá)及其促膽固醇流出的作用,胞內(nèi)脂質(zhì)蓄積和泡沫細(xì)胞形成明顯加劇。結(jié)論:(1)omentin-1通過(guò)pi3k/akt途徑增加人thp-1巨噬細(xì)胞lxrα和abca1表達(dá),促進(jìn)脂質(zhì)流出,抑制巨噬細(xì)胞內(nèi)脂質(zhì)蓄積和泡沫細(xì)胞形成。第3章omentin-1對(duì)apoe-/-小鼠動(dòng)脈粥樣硬化的影響目的:探討omentin-1對(duì)apoe-/-小鼠體內(nèi)rct、血脂水平、主動(dòng)脈壁的脂質(zhì)沉積,以及對(duì)粥樣硬化病變的影響和機(jī)制。方法:采用高脂飲食(含15%豬油+0.25%膽固醇)喂飼的45只apoe-/-小鼠,并隨機(jī)地分為三組,分別為:高脂對(duì)照組、omentin-1組、omentin-1+ly2940029組。omentin-1組腺病毒轉(zhuǎn)染omentin-1以1×108pfu/kg(pfu:空斑形成單位),ome+ly組小鼠再加以20mg/kgpi3k抑制劑ly2940029,溶入0.2ml的生理鹽水中進(jìn)行尾靜脈注射,每2周注射一次,都用基礎(chǔ)飲食加上高脂高膽固醇(15%豬油+0.25%膽固醇)喂養(yǎng),直至實(shí)驗(yàn)結(jié)束,共處理8周。采用液體閃爍計(jì)數(shù)以測(cè)定mpm來(lái)源的rct效率;采用酶氧化法檢測(cè)甘油三酯(tg)、總膽固醇、高密度脂蛋白膽固醇(hdl-c)及低密度脂蛋白膽固醇(ldl-c)等血脂水平;采用蘇丹Ⅳ染色以顯示主動(dòng)脈內(nèi)膜的as病變情況;采用he染色顯示主動(dòng)脈竇的as病變情況;采用油紅o染色以觀察主動(dòng)脈竇處脂質(zhì)沉積的情況;采用masson三色染色以顯示斑塊中的膠原纖維;采用westernblot檢測(cè)小鼠的主動(dòng)脈abca1等蛋白的表達(dá)。結(jié)果:輸注了轉(zhuǎn)染omentin-1的質(zhì)粒明顯增強(qiáng)了apoe-/-小鼠糞便中3h固醇的放射活性,并增高血漿的hdl-c水平,降低了ldl-c水平,使主動(dòng)脈內(nèi)膜的as病變面積減小,減少主動(dòng)脈竇處的脂質(zhì)沉積,增強(qiáng)as斑塊的穩(wěn)定性,增加了主動(dòng)脈abca1的蛋白表達(dá)。注射ly2940029則明顯減少糞便中的固醇水平,增加主動(dòng)脈壁內(nèi)脂質(zhì)沉積,促進(jìn)動(dòng)脈粥樣硬化病變的發(fā)展,下調(diào)abca1蛋白表達(dá)。結(jié)論:(1)omentin-1促進(jìn)apoe-/-鼠體內(nèi)rct和升高血漿hdl-c水平。(2)omentin-1抑制apoe-/-鼠主動(dòng)脈脂質(zhì)沉積,延緩粥樣硬化病變的進(jìn)展。(3)omentin-1增強(qiáng)apoe-/-鼠主動(dòng)脈壁組織的abca1表達(dá),并且其可能是通過(guò)pi3k/akt信號(hào)通路而起調(diào)節(jié)作用的。第4章丹參酮iia對(duì)巨噬細(xì)胞omentin-1/abca1水平及apoe-/-小鼠主動(dòng)脈病變的影響及其機(jī)制目的:觀察丹參酮iia(tanshinoneiia,tan)對(duì)thp-1巨噬細(xì)胞中omentin-1和abca1表達(dá),以及對(duì)apoe-/-小鼠體內(nèi)血脂水平、rct、主動(dòng)脈壁as病變的影響,并探討tan抗as的作用機(jī)制。方法:用tan處理thp-1巨噬細(xì)胞,并結(jié)合omentin-1sirna轉(zhuǎn)染thp-1巨噬細(xì)胞后,采用實(shí)時(shí)熒光定量pcr以檢測(cè)omentin-1和abca1水平,采用westernblot檢測(cè)omentin-1和abca1蛋白表達(dá);采用液體閃爍計(jì)數(shù)以測(cè)定荷脂THP-1巨噬細(xì)胞內(nèi)的膽固醇流出情況,采用HPLC檢測(cè)細(xì)胞內(nèi)脂質(zhì)的含量。高脂飲食(含15%豬油+0.25%膽固醇)喂飼的45只apoE-/-小鼠被隨機(jī)分為三組,分別為:高脂對(duì)照組、丹參酮IIA組和丹參酮IIA+Omentin-1 siRNA組。采用液體閃爍計(jì)數(shù)以測(cè)定MPM來(lái)源的RCT效率,采用酶氧化法以檢測(cè)TG、TC、HDL-c和LDL-c等的血脂水平,采用蘇丹Ⅳ染色以顯示主動(dòng)脈內(nèi)膜的As病變情況,采用HE染色以顯示主動(dòng)脈竇As病變情況,采用油紅O染色以顯示主動(dòng)脈竇處脂質(zhì)的沉積情況,采用Masson三色染色以顯示As斑塊中的膠原纖維情況。結(jié)果:觀察到Tan可以呈劑量和時(shí)間依賴性地增強(qiáng)了THP-1巨噬細(xì)胞中Omentin-1和ABCA1蛋白的表達(dá),增強(qiáng)細(xì)胞內(nèi)膽固醇流出,并減少細(xì)胞內(nèi)的FC、CE和TC含量。Tan可增強(qiáng)apoE-/-小鼠糞便中3H膽固醇的放射活性,并增高血漿HDL-c水平,降低LDL-c水平,增強(qiáng)主動(dòng)脈Omentin-1和ABCA1表達(dá),減少了主動(dòng)脈內(nèi)膜的As變面積,減輕了主動(dòng)脈竇處的脂質(zhì)沉積,增強(qiáng)了斑塊的穩(wěn)定性。抑制Omentin-1表達(dá)后,則明顯削弱Tan的上述作用。結(jié)論:(1)Tan抗As的作用與增強(qiáng)巨噬細(xì)胞內(nèi)膽固醇外流和體內(nèi)的RCT功能密切相關(guān)。(2)Tan抗As的作用機(jī)制與升高Omentin-1水平并進(jìn)而增加ABCA1表達(dá)有關(guān),并且可能是通過(guò)PI3K/Akt信號(hào)通路而起調(diào)節(jié)作用的。
[Abstract]:Atherosclerosis (As) is in the forefront of the global morbidity and mortality rate, which seriously endangers human health. In the early stage of atherosclerosis, its marked pathological feature was the accumulation of lipid and the formation of foam cells in a large number of macrophages under vascular endothelium. Internal cholesterol, the most important component of atherosclerotic plaques, promotes the further progress of atherosclerosis. Therefore, it promotes cholesterol outflow in macrophages and reverse cholesterol transport (RCT) in vivo, which inhibits the formation of foamy cells and the lipid deposition in the blood vessel wall. Adenosine triphosphate binding cassette transporter A1 (ATP binding cassette transporter A1, ABCA1) is a membrane integrin that transships intracellular free cholesterol and phospholipids to the outer side of the cell membrane with ATP as a source of energy and eventually combines with the apolipoprotein AI (apoprotein AI, apoAI) attached to the surface of the cell. The formation of high density lipoprotein (HDL), which is a necessary process for HDL production, is also a key step in promoting excessive cholesterol Exodus in macrophages and the key step in RCT, the expression of.Abca1 in macrophages and its activity often finely regulated by the transcriptional and post transcriptional levels. The omentin (omentin) is a HDL. A newly discovered class of adipocyte factors, mainly expressed and released from omentum adipose tissue. It is worth noting that this gene has been found to regulate glucose uptake. Patients with obesity or obesity related diseases, including type 2 diabetes, endothelial dysfunction, carotid atherosclerosis, and coronary artery disease, have been found to be in the plasma omentin-1 level. Lower. Studies have shown that omentin-1 is positively related to high density lipoprotein cholesterol (HDL-C) and is negatively correlated with glucose and triglyceride levels. Patients with abnormal circulating omentin-1 levels in the early stage of metabolic syndrome (MetS) have a higher risk of developing diabetes and cardiovascular disease. Therefore, omentin-1 is closely related to metabolic syndrome, in metabolism. The discovery of.Omentin-1 in the occurrence and development of atherosclerosis in patients with RCT, the discovery of differential expression in lipid metabolism and as provides us with new ways and perspectives. Therefore, omentin-1 is expected to become one of the cardiovascular protective factors and intervention targets. However, omentin-1 is expressed in ABCA1 and leads to the improvement of HDL function and bile. In this study, we studied the role of omentin-1 on the expression of ABCA1 in macrophages and the potential molecular mechanism in this study. In order to explore the mechanism of omentin-1 anti atherosclerosis, we first observed the expression of ABCA1 and intracellular cholesterol in THP-1 macrophages in the first part of the experiment. The effect of outflow and lipid content. In the second experiment, we explored the mechanism of omentin-1 mediated THP-1 macrophage ABCA1 expression and cholesterol efflux. Then, in the third experiment, we observed the effects of omentin-1 on blood lipid levels, cholesterol reverse transport and atherosclerotic lesions in apoe-/- mice. In the fourth experiment, we observed the expression of omentin-1 and ABCA1 in macrophages, lipid metabolism, and the effect on atherosclerotic lesions of apoe-/- mice, which had strong lipid regulating effect, and studied the mechanism of the anti atherosclerosis mechanism of Tan by up regulation of omentin-1. This study was to study the mechanism of the anti atherosclerosis of Tan by up regulation of omentin-1. The anti atherosclerotic effect and mechanism of omentin-1 may provide new prevention and treatment targets for atherosclerotic disease. First the effect of omentin-1 on ABCA1 expression and cholesterol efflux of THP-1 macrophages is to observe the expression level of abca1mrna and protein in THP-1 macrophages, intracellular cholesterol efflux and lipids. Methods: after the treatment of THP-1 derived macrophages with omentin-1 and / or LXR alpha siRNA, the expression of abca1mrna in the cells of each experimental group was detected by RT-PCR, the level of ABCA1 protein was detected by Westernblot, and the content of intracellular total cholesterol (TC) free cholesterol (FC) and cholesteryl ester (CE) was detected by HPLC, and the liquid scintillation counting instrument was used to detect the internal gallbladder. Results: omentin-1 showed time and concentration dependent increase of ABCA1 expression in macrophages, promoted intracellular cholesterol efflux, reduced intracellular TC, FC and Ce content, inhibited intracellular lipid accumulation and foam cell formation, while abca1sirna and omentin-1 co treated cells significantly inhibited omentin-1 promoted by abca1sirna and omentin-1. The effect of cholesterol outflow, intracellular lipid accumulation and foam cell formation increased obviously. Conclusion: (1) omentin-1 increases the abca1mrna and protein expression of THP-1 macrophages. (2) omentin-1 promotes lipid efflux of ABCA1 mediated THP-1 macrophages and inhibits lipid accumulation and foam cell formation in macrophages. Second chapter omentin-1 mediates THP-1 meagage The mechanism of the action mechanism of ABCA1 expression and cholesterol efflux: To explore the mechanism of omentin-1 mediated ABCA1 expression and cholesterol efflux in THP-1 macrophages. Methods: omentin-1 or LXR alpha siRNA, pi3ksirna, aktsirna, PI3K inhibitor ly2940029 and Akt inhibitors were used to detect the derived macrophages. R alpha protein level, HPLC detection of intracellular total cholesterol (TC) free cholesterol (FC) and cholesteryl ester (CE) content, liquid scintillation counting apparatus to detect intracellular cholesterol efflux, oil red O staining to observe the intracellular lipid droplets. Results: omentin-1 increases the expression of ABCA1 in macrophages, promotes intracellular cholesterol efflux, reduces intracellular TC, FC and Ce content, inhibits intracellular. Lipid accumulation and foam cell formation. After adding LXR alpha siRNA, pi3ksirna, aktsirna, PI3K inhibitor ly2940029 and Akt inhibitor HimO and omentin-1 co processing cells, the expression of ABCA1 and the effect of cholesterol efflux were inhibited, and the accumulation of intracellular lipids and the formation of foam cells were obviously intensified. Conclusion: (1) omentin-1 through pi3k/akt. Diameter increases the expression of LXR alpha and ABCA1 in human THP-1 macrophages, promotes lipid outflow, inhibits lipid accumulation in macrophages and foams cell formation. Third the effects of omentin-1 on atherosclerosis in apoe-/- mice: the study of omentin-1 on RCT, lipid levels, lipid deposition in the aortic wall and atherosclerosis in apoe-/- mice Methods: 45 apoe-/- mice fed with high fat diet (containing 15% lard +0.25% cholesterol) were randomly divided into three groups: high fat control group, omentin-1 group, omentin-1+ly2940029 group.Omentin-1 adenovirus transfected omentin-1 with 1 x 108pfu/kg (pfu: empty plaque formation unit), ome+ly group mice then 20mg/kgpi3k The inhibitor ly2940029, injected into the normal saline of 0.2ml, injected the tail vein every 2 weeks, fed the basal diet plus high fat and high cholesterol (15% lard +0.25% cholesterol), until the end of the experiment, for 8 weeks. The liquid scintillation counting was used to determine the RCT efficiency of the MPM source, and the enzyme oxidation method was used to detect triglyceride (TG), general Cholesterol, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) and other blood lipid levels; Sultan IV staining was used to show the as lesion of the aortic intima; he staining was used to display the as lesion of the aortic sinus, and the oil red O staining was used to observe the lipid deposition in the aortic sinus; Masson trichromatic staining was used. The expression of ABCA1 and other proteins in the aorta of the mice was detected by Westernblot. Results: the transfection of omentin-1 transfected plasmid significantly enhanced the radioactivity of 3H sterol in the feces of apoe-/- mice, increased the level of HDL-C in plasma, reduced the LDL-C level, reduced the as lesion area of the aorta intima, and reduced the lesion area of the aorta intima. The lipid deposition at the sinus of aortic sinus enhanced the stability of as plaque and increased the protein expression of ABCA1 in the aorta. Injection of ly2940029 significantly reduced the level of sterol in the feces, increased the lipid deposition in the aortic wall, promoted the development of atherosclerotic lesions, and lowered the expression of ABCA1 protein. Conclusion: (1) omentin-1 promotes RCT in the body of apoe-/- mice. Increase the plasma HDL-C level. (2) omentin-1 inhibits the aortic lipid deposition in apoe-/- rats and delays the progression of atherosclerotic lesions. (3) ABCA1 expression in the aorta wall of apoe-/- rats is enhanced by omentin-1, and it may be regulated by the pi3k/akt signaling pathway. The fourth chapter of tanshinone IIA to macrophage omentin-1/abca1 level and apoe-/ Effect and mechanism of mouse aortic disease: To observe the expression of tanshinone IIA (tanshinoneIIA, tan) on omentin-1 and ABCA1 in THP-1 macrophages, as well as the effect on serum lipid level, RCT, as lesion of the aortic wall in apoe-/- mice, and to explore the mechanism of Tan as on tan. After transfection of RNA to THP-1 macrophages, real-time fluorescence quantitative PCR was used to detect the level of omentin-1 and ABCA1. The expression of omentin-1 and ABCA1 protein was detected by Westernblot; liquid scintillation counting was used to determine the cholesterol efflux in the lipid THP-1 macrophages. The content of intracellular lipids was detected by HPLC. High fat diet (containing 15% lard +0.25%) was used. 45 apoE-/- mice fed with cholesterol were randomly divided into three groups: the high fat control group, the tanshinone IIA group and the tanshinone IIA+Omentin-1 siRNA group. The liquid scintillation counting was used to determine the RCT efficiency of the MPM source. The lipid levels of TG, TC, HDL-c and LDL-c were detected by enzyme oxidation, and the Sultan IV staining was used to display the internal aorta. The As lesion of the membrane was used to display the As lesion of the aortic sinus by HE staining. The oil red O staining was used to show the deposition of lipid in the aortic sinus, and the Masson stain was used to show the collagen fiber in the As plaque. The results showed that Tan could be dosed and time dependent on the increase of Omentin-1 and A in THP-1 macrophages. The expression of BCA1 protein, the increase of intracellular cholesterol efflux, and the reduction of the intracellular FC, CE and TC content.Tan can enhance the radioactivity of 3H cholesterol in the apoE-/- mice, increase the level of HDL-c, reduce the LDL-c level, increase the expression of Omentin-1 and ABCA1 in the aorta, reduce the area of the intima intima of the aorta, and reduce the sinus of the aortic sinus. Lipid deposition enhanced the stability of plaque. After inhibiting the expression of Omentin-1, the effect of Tan was obviously weakened. Conclusion: (1) the anti As effect of Tan is closely related to the enhancement of cholesterol Exodus in macrophages and the function of RCT in the body. (2) the mechanism of the anti As action of Tan is related to the increase of Omentin-1 level and the increase of ABCA1 expression, and may be associated with As. It is regulated by the PI3K/Akt signaling pathway.
【學(xué)位授予單位】：南華大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R543.5

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 ;豚鼠巨噬細(xì)胞經(jīng)P_(204)處理后的抗石英細(xì)胞毒作用[J];國(guó)外醫(yī)學(xué)參考資料(衛(wèi)生學(xué)分冊(cè));1976年04期

2 鄧俠進(jìn);;巨噬細(xì)胞的抗癌作用[J];遵義醫(yī)學(xué)院學(xué)報(bào);1979年02期

3 陸天才;;疾病對(duì)肺巨噬細(xì)胞的影響[J];煤礦醫(yī)學(xué);1982年01期

4 郭瑞清;祝彼得;;一種分離巨噬細(xì)胞的簡(jiǎn)單方法[J];濱州醫(yī)學(xué)院學(xué)報(bào);1990年02期

5 謝志堅(jiān);巨噬細(xì)胞異質(zhì)性[J];醫(yī)學(xué)綜述;2001年06期

6 饒艷;運(yùn)動(dòng)及神經(jīng)內(nèi)分泌對(duì)巨噬細(xì)胞功能的調(diào)節(jié)[J];體育與科學(xué);2002年05期

7 朱金元;;吸煙對(duì)肺巨噬細(xì)胞的影響[J];浙江醫(yī)學(xué)教育;2003年01期

8 張俊峰;過(guò)氧化物酶體增殖物激活受體與單核/巨噬細(xì)胞系[J];醫(yī)學(xué)綜述;2004年03期

9 韋錦學(xué);顧軍;;巨噬細(xì)胞的激活誘導(dǎo)死亡[J];生命科學(xué);2006年02期

10 李曉曦;郭寧;曹雪濤;;腫瘤相關(guān)巨噬細(xì)胞促進(jìn)腫瘤生長(zhǎng)與轉(zhuǎn)移的研究現(xiàn)狀[J];中國(guó)腫瘤生物治療雜志;2008年01期

相關(guān)會(huì)議論文 前10條

1 史玉玲;王又明;豐美福;;巨噬細(xì)胞激活作用的研究[A];中國(guó)細(xì)胞生物學(xué)學(xué)會(huì)第五次會(huì)議論文摘要匯編[C];1992年

2 吳國(guó)明;周輝;;巨噬細(xì)胞和創(chuàng)傷纖維化[A];2009年浙江省骨科學(xué)學(xué)術(shù)年會(huì)論文匯編[C];2009年

3 李奇;王海杰;;透明質(zhì)酸對(duì)于淋巴結(jié)巨噬細(xì)胞運(yùn)動(dòng)的影響[A];解剖學(xué)雜志——中國(guó)解剖學(xué)會(huì)2002年年會(huì)文摘匯編[C];2002年

4 劉革修;歐大明;劉軍花;黃紅林;廖端芳;;丙丁酚在體外能抑制巨噬細(xì)胞脂質(zhì)氧化介導(dǎo)的低密度脂蛋白氧化并調(diào)節(jié)氧化巨噬細(xì)胞的分泌功能[A];面向21世紀(jì)的科技進(jìn)步與社會(huì)經(jīng)濟(jì)發(fā)展（下冊(cè)）[C];1999年

5 葉金善;楊麗霞;郭瑞威;;環(huán)氧化酶-2/前列腺素E_2在血管緊張素Ⅱ刺激巨噬細(xì)胞表達(dá)細(xì)胞外基質(zhì)金屬蛋白酶誘導(dǎo)因子中的作用[A];第十三次全國(guó)心血管病學(xué)術(shù)會(huì)議論文集[C];2011年

6 秦帥;陳希;孔德明;;構(gòu)建由綠色熒光標(biāo)記巨噬細(xì)胞的轉(zhuǎn)基因斑馬魚(yú)系[A];貴州省中西醫(yī)結(jié)合內(nèi)分泌代謝學(xué)術(shù)會(huì)論文匯編[C];2012年

7 武劍華;徐惠綿;;腫瘤相關(guān)巨噬細(xì)胞在胃癌中的相關(guān)研究[A];第9屆全國(guó)胃癌學(xué)術(shù)會(huì)議暨第二屆陽(yáng)光長(zhǎng)城腫瘤學(xué)術(shù)會(huì)議論文匯編[C];2014年

8 何軍;;血凝素樣氧化型低密度脂蛋白受體升高巨噬細(xì)胞內(nèi)膽固醇水平[A];中華醫(yī)學(xué)會(huì)第11次心血管病學(xué)術(shù)會(huì)議論文摘要集[C];2009年

9 宋盛;周非凡;邢達(dá);;PDT誘導(dǎo)的凋亡細(xì)胞對(duì)巨噬細(xì)胞NO合成的影響[A];第七屆全國(guó)光生物學(xué)學(xué)術(shù)會(huì)議論文摘要集[C];2010年

10 張磊;朱建華;黃元偉;姚航平;;血管緊張素Ⅱ?qū)奘杉?xì)胞(THP-1重細(xì)胞)凝集素樣氧化低密度脂蛋白受體表達(dá)的影響[A];浙江省免疫學(xué)會(huì)第五次學(xué)術(shù)研討會(huì)論文匯編[C];2004年

相關(guān)重要報(bào)紙文章 前10條

1 通訊員 李靜 記者 胡德榮;惡性腫瘤巨噬細(xì)胞未必皆“惡人”[N];健康報(bào);2014年

2 蘭克;以嘗試用巨噬細(xì)胞治癱瘓[N];科技日?qǐng)?bào);2000年

3 薛佳;免疫系統(tǒng)——人體的“衛(wèi)士”[N];保健時(shí)報(bào);2009年

4 記者 胡德榮;鐵泵蛋白“維穩(wěn)”鐵代謝作用首次闡明[N];健康報(bào);2011年

5 侯嘉 何新鄉(xiāng);硒的神奇功能[N];中國(guó)食品質(zhì)量報(bào);2003年

6 唐穎 倪兵 陳代杰;巨噬細(xì)胞泡沫化抑制劑研究快步進(jìn)行[N];中國(guó)醫(yī)藥報(bào);2006年

7 劉元江;新發(fā)現(xiàn)解釋腫瘤為何易成“漏網(wǎng)之魚(yú)”[N];醫(yī)藥經(jīng)濟(jì)報(bào);2007年

8 本報(bào)記者 侯嘉 通訊員 何新鄉(xiāng);今天你補(bǔ)硒了嗎[N];醫(yī)藥經(jīng)濟(jì)報(bào);2003年

9 左志剛;升血小板藥使用注意[N];醫(yī)藥養(yǎng)生保健報(bào);2007年

10 記者 許琦敏;“鐵泵”蛋白幫助回收鐵元素[N];文匯報(bào);2011年

相關(guān)博士學(xué)位論文 前10條

1 周赤燕;巨噬細(xì)胞MsrA對(duì)動(dòng)脈粥樣硬化的干預(yù)研究[D];武漢大學(xué);2013年

2 章桂忠;TIPE2蛋白調(diào)控細(xì)胞增殖和炎癥的機(jī)制研究[D];山東大學(xué);2015年

3 張瑜;DKK1抑制巨噬細(xì)胞內(nèi)脂質(zhì)沉積及其相關(guān)分子機(jī)制[D];山東大學(xué);2015年

4 孟濤;異丙酚對(duì)心臟收縮功能的抑制作用及其對(duì)巨噬細(xì)胞分泌功能調(diào)節(jié)的機(jī)制研究[D];山東大學(xué);2015年

5 周興;基于酵母微囊構(gòu)建新型口服巨噬細(xì)胞靶向遞送系統(tǒng)的研究[D];第三軍醫(yī)大學(xué);2015年

6 蔣興偉;Tim-3對(duì)巨噬細(xì)胞極化的調(diào)控機(jī)制研究[D];中國(guó)人民解放軍軍事醫(yī)學(xué)科學(xué)院;2015年

7 劉伯玉;清道夫受體A介導(dǎo)小鼠巨噬細(xì)胞吞噬鉤端螺旋體研究[D];上海交通大學(xué);2013年

8 楊紹俊;miRNA-155介導(dǎo)ESAT-6誘導(dǎo)巨噬細(xì)胞凋亡的分子機(jī)制及其在結(jié)核診斷中的作用[D];第三軍醫(yī)大學(xué);2015年

9 翟光耀;單核/巨噬細(xì)胞Ly6C~(low)亞群在心肌梗死后瘢痕形成期的抗炎特性研究[D];北京協(xié)和醫(yī)學(xué)院;2014年

10 韓露;TRB3介導(dǎo)的脂肪組織巨噬細(xì)胞極化與糖尿病冠狀動(dòng)脈病變關(guān)系的研究[D];山東大學(xué);2015年

相關(guān)碩士學(xué)位論文 前10條

1 馬春梅;AP0E~(-/-)小鼠TLR9介導(dǎo)巨噬細(xì)胞極化效應(yīng)對(duì)動(dòng)脈粥樣硬化作用的研究[D];福建醫(yī)科大學(xué);2015年

2 張譯丹;鹽皮質(zhì)激素受體拮抗劑調(diào)控巨噬細(xì)胞表型對(duì)實(shí)驗(yàn)性矽肺的作用[D];河北醫(yī)科大學(xué);2015年

3 盧文冉;HCV core蛋白作用的巨噬細(xì)胞培養(yǎng)上清對(duì)肝細(xì)胞生物學(xué)性狀的影響[D];河北醫(yī)科大學(xué);2015年

4 李文建;載脂蛋白E影響巨噬細(xì)胞因子表達(dá)及分型的機(jī)制研究[D];河北醫(yī)科大學(xué);2015年

5 曹爽;高糖對(duì)巨噬細(xì)胞TLR4信號(hào)轉(zhuǎn)導(dǎo)的調(diào)節(jié)作用[D];河北醫(yī)科大學(xué);2015年

6 寧程程;腫瘤相關(guān)巨噬細(xì)胞在子宮內(nèi)膜癌雌激素敏感性中的作用及機(jī)制研究[D];復(fù)旦大學(xué);2014年

7 高龍;PLD4在腫瘤相關(guān)巨噬細(xì)胞抑制結(jié)腸癌增殖中的作用研究[D];成都醫(yī)學(xué)院;2015年

8 任虹;感染期子宮頸癌U14細(xì)胞荷瘤小鼠抑制巨噬細(xì)胞CCL5分泌的機(jī)制研究[D];河北醫(yī)科大學(xué);2015年

9 李美玲;雙酚A對(duì)小鼠腹腔巨噬細(xì)胞極化影響的體外研究[D];安徽醫(yī)科大學(xué);2015年

10 劉瓊;黃芪多糖影響巨噬細(xì)胞向脂肪細(xì)胞趨化的作用及機(jī)制研究[D];新鄉(xiāng)醫(yī)學(xué)院;2015年

，

本文編號(hào)：1913510