發(fā)布時(shí)間：2018-06-12 03:22

  本文選題：動(dòng)脈粥樣硬化 + α-亞麻酸植物甾醇酯　； 參考：《華中科技大學(xué)》2015年博士論文

【摘要】：目的：探討α-亞麻酸植物甾醇酯(a-linolenic acid ester of plant sterol, ALA-PS)對(duì)高脂飼料喂養(yǎng)載脂蛋白E基因敲除(apol ipoprote i n E knockout, ApoE KO)小鼠動(dòng)脈粥樣硬化(atherosclerosis, AS)的保護(hù)作用及相關(guān)分子機(jī)制。 方法：將42只ApoE KO小鼠(6周齡,雄性,體重12-15g)隨機(jī)分為3組,即高脂飼料組(high fat diet, HFD),亞麻油干預(yù)組(flaxseed oil, FO)和亞麻油添加a-亞麻酸植物甾醇酯干預(yù)組(FO+ALA-PS)。 HFD組給予高脂飼料(脂肪21%,膽固醇0.15%,蛋白質(zhì)200%)：FO組給予相同的高脂飼料和5%亞麻油；FO+ALA-PS組給予相同的高脂飼料并添加2.6%亞麻油和3.3%ALA-PS。對(duì)照組(Control)為14只相同遺傳背景下的野生型C57BL/6小鼠,給予普通飼料喂養(yǎng),實(shí)驗(yàn)周期為18周。 結(jié)果： 1、主動(dòng)脈整體、主動(dòng)脈竇和主動(dòng)脈弓油紅O及HE染色結(jié)果顯示,與對(duì)照組小鼠相比,HFD組小鼠血管內(nèi)壁可見大面積AS斑塊形成。ALA-PS干預(yù)后顯著減少AS斑塊面積(P0.05)。免疫組織化學(xué)染色結(jié)果顯示,ALA-PS明顯改善HFD誘導(dǎo)的巨噬細(xì)胞和單核細(xì)胞聚集浸潤以及血管平滑肌細(xì)胞增殖與遷移。 2、HFD誘導(dǎo)脂代謝紊亂。ALA-PS干預(yù)顯著改善血脂異常以及肝臟總膽固醇(total cholesterol, TC)和甘油三酯(triglyceride, TG)水平升高(P0.05)。并且,明顯升高肝臟低密度脂蛋白受體(LDLr)、清道夫受體(SR-BI)和膽固醇外流關(guān)鍵因子腺苷三磷酸結(jié)合核轉(zhuǎn)運(yùn)受體Al (ABCA1)、肝臟X受體-α(LXRa)mRNA和蛋白的表達(dá)水平以及明顯降低小鼠肝臟膽固醇合成關(guān)鍵因子羥甲基戊二酸單酰輔酶A還原酶(HMGCR)和膽固醇調(diào)節(jié)元件結(jié)合蛋白-2(SREBP-2) mRNA和蛋白的表達(dá)水平(P0.05)。此外,ALA-PS干預(yù)顯著增加脂肪酸β-氧化關(guān)鍵因子過氧化物酶體增殖物激活受體-α (PPARa)、肉毒堿棕櫚�；D(zhuǎn)移酶1A (CPT1A)和乙酰輔酶A氧化酶1(ACOXI) mRNA和蛋白的表達(dá)水平,并顯著降低調(diào)控脂質(zhì)新生關(guān)鍵因子膽固醇調(diào)節(jié)元件結(jié)合蛋白-1(SREBP-1)和乙酰輔酶A羧化酶(ACC) mRNA和蛋白的表達(dá)水平(P0.05)。 3、HFD誘導(dǎo)炎癥反應(yīng)增加。ALA-PS干預(yù)能夠顯著降低血漿炎癥因子IL-1β、IL-6. TNF-α、 MCP-1、 sVCAM-1和sIC AM-1的水平,并且明顯抑制小鼠主動(dòng)脈IL-1β、 IL-6、 TNF-α、 MCP-1、 VCAM-1和ICAM-1mRNA和蛋白的表達(dá)水平升高(P0.05)。同時(shí),顯著降低小鼠外周血單核細(xì)胞IL-1β、 IL-6、 TNF-a和MCP-1mRNA和蛋白的表達(dá)水平(P0.05)。 4、HFD誘導(dǎo)機(jī)體氧化應(yīng)激。ALA-PS干預(yù)能夠有效地降低血清和肝臟MDA含量并增加GSH水平,同時(shí)顯著抑制主動(dòng)脈ROS產(chǎn)生(P0.05)。并且,ALA-PS干預(yù)顯著減少小鼠主動(dòng)脈NADPH氧化酶亞基P22phox、 p47phox、 p67phox和gp91phox mRNA和蛋白表達(dá)(P0.05)。 結(jié)論：α-亞麻酸植物甾醇酯對(duì)動(dòng)脈粥樣硬化具有保護(hù)作用,其機(jī)制與改善脂代謝、調(diào)節(jié)炎癥反應(yīng)以及抑制氧化應(yīng)激有關(guān)。
[Abstract]:Objective: to investigate the protective effect of 偽 -linolenic acid ester of plant sterol, ALA-PS) on Apolipoprotein E knockout (ApoE KOA) gene knockout (ApoEKOA) mice fed high fat diet. Methods: the protective effect of 偽 -linolenic acid ester of plant sterol, ALA-PSN on atherosclerotic atherosclerosis (ASA) in mice fed with high fat diet was studied. : 42 ApoE KO mice aged 6 weeks, Male, weight 12-15 g) were randomly divided into three groups: high fat dietate, HFDD, flax seed oil (FOO) and FO ALA-PSN treated with flax oil. The HFD group was given the same high fat diet (fat 21, cholesterol 0.15, protein 200: FO) and 5% linseed oil FO ALA-PS with the same high fat diet and 2.6% linseed oil and 3.3 ALA-PSs. The control group was 14 wild-type C57BL / 6 mice with the same genetic background, fed with common diet for 18 weeks. Results: 1. The results showed that: 1, the whole aorta, aortic sinus and aortic arch were stained with oil red O and HE. Compared with the control group, large area of as plaque formation was observed in the intravascular wall of HFD group. ALA-PS significantly decreased as plaque area (P0.05) after intervention. The results of immunohistochemical staining showed that ALA-PS significantly improved the aggregation and infiltration of macrophages and monocytes induced by HFD and the proliferation and migration of vascular smooth muscle cells. Total cholesterol (TCc) and triglyceride (TGG) levels increased P0.05. And, The expression of LDLrN, SR-BI), the key factor of cholesterol efflux, adenosine triphosphate binding nuclear transport receptor, the expression of liver X receptor-偽 -LXRaN mRNA and protein, and the decrease of liver bile duct in mice were significantly increased, and the key factors of cholesterol efflux, adenosine triphosphate binding nuclear transport receptor, liver X receptor-偽 -LXRaN mRNA and protein expression were significantly increased. The expression levels of HMGCR-HMGCRand cholesterol regulatory element binding protein-SREBP-2 mRNA and protein in steroid synthesis key factor hydroxymethyl glutaric acid monoacyl coA reductase A reductase (HMGCR-HMGCRA) and cholesterol regulatory element binding protein-SREBP-2 were found to be P0.05a. In addition, ALA-PS significantly increased the expression levels of PPARaA, carnitine palmitoyltransferase 1A (CPT1A) and acetyl-coA oxidase 1 (ACOXI) mRNA and protein in peroxisome proliferator activator receptor (PPARaA) and acetyl coA oxidase (ACOA oxidase 1). The levels of mRNA and protein expression of cholesterol regulatory element binding protein-1 (SREBP-1) and acetyl-coA carboxylase (ACC-1) were significantly decreased. The levels of TNF- 偽, MCP-1, sVCAM-1 and sIC AM-1 were significantly inhibited, and the expression levels of IL-1 尾, IL-6, TNF- 偽, MCP-1, VCAM-1 and ICAM-1 mRNA and protein in aorta of mice were significantly increased (P 0.05). At the same time, the expression of IL-1 尾, IL-6, TNF-a and MCP-1 mRNA and protein in peripheral blood monocytes of mice was significantly decreased. 4. The intervention of HFD induced by oxidative stress could effectively reduce the MDA content and increase the level of GSH in serum and liver, and significantly inhibit the production of P0.05 by aortic Ros. ALA-PS significantly reduced the expression of NADPH oxidase subunits P22phox, p47phox, p67phox and gp91phox mRNA and protein in mouse aorta. Conclusion: phytosterol 偽 -linolenic acid has protective effect on atherosclerosis, and its mechanism and lipid metabolism are improved. Regulation of inflammation and inhibition of oxidative stress.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類號(hào)】：R151
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本文編號(hào)：2008074