【摘要】：動(dòng)脈粥樣硬化是多種心腦血管疾病的病理基礎(chǔ)。動(dòng)脈粥樣硬化的發(fā)病機(jī)制主要有血脂代謝異常、炎癥反應(yīng)、內(nèi)皮損傷、氧化應(yīng)激等。高密度脂蛋白(High density lipoprotein, HDL)能夠通過(guò)膽固醇逆轉(zhuǎn)運(yùn)(Reverse cholesterol transport, RCT)、抗炎、抗氧化、抗血栓、抗細(xì)胞凋亡及舒張血管來(lái)實(shí)現(xiàn)保護(hù)血管、抗動(dòng)脈粥樣硬化的功能。而最新的研究發(fā)現(xiàn)單純HDL水平不能反映其抗動(dòng)脈粥樣硬化功能,而HDL的功能與其亞型、代謝、組成成分密切相關(guān)。HDL的亞型分布、組分和功能開(kāi)始成為目前抗動(dòng)脈粥樣硬化研究的熱點(diǎn)。ApoA-Ⅰ是HDL的主要組成蛋白和結(jié)構(gòu)基礎(chǔ),也是HDL完成RCT、抗內(nèi)皮細(xì)胞凋亡、抗氧化、抗炎功能的主要承擔(dān)者。ApoA-Ⅰ數(shù)量減少或結(jié)構(gòu)改變,HDL原有功能則會(huì)減弱或喪失,甚至出現(xiàn)促AS作用。HDL經(jīng)由preβ1-HDL→HDL3→HDL2的過(guò)程而逐漸成熟,HDL2作為大的成熟HDL亞型顆粒,可促使膽固醇向肝臟和合成類固醇激素的組織轉(zhuǎn)運(yùn),低HDL2水平與冠心病的風(fēng)險(xiǎn)負(fù)相關(guān)。三磷酸腺苷結(jié)合盒轉(zhuǎn)運(yùn)子A1(ATP-binding cassette transporters A1, ABCA1)能夠與HDL結(jié)合,促進(jìn)細(xì)胞內(nèi)膽固醇的流出,影響HDL顆粒生成,參與RCT,調(diào)節(jié)脂質(zhì)代謝。此外,ABCA1還可通過(guò)抑制炎癥因子表達(dá)、參與氧化應(yīng)激反應(yīng)等多種途徑影響AS進(jìn)程。B類Ⅰ型清道夫受體(Scavenger receptor class B, type Ⅰ, SR-BI)能夠選擇性攝取HDL中的膽固醇酯,傳遞給肝臟和類固醇激素生成組織,完成RCT；還能夠介導(dǎo)外周細(xì)胞膽固醇流出過(guò)程,參與多種脂蛋白的代謝。髓過(guò)氧化物酶(Myeloperoxidase, MPO)和對(duì)氧磷酶1(Paraoxonase 1,PON1)是HDL影響炎癥、氧化應(yīng)激的相關(guān)蛋白。MPO能夠選擇性氧化修飾ApoA-Ⅰ,使HDL功能減弱或喪失,加速AS斑塊發(fā)展。相反,PON1能夠直接參與脂蛋白中過(guò)氧化物的水解,使HDL免受氧化修飾,保護(hù)HDL的抗氧化功能。卵磷脂膽固醇酰基轉(zhuǎn)移酶(Lecithin cholesterol acyltransf erase, LCAT)可以將膽固醇酯化,使膽固醇不斷進(jìn)入到HDL中,使HDL逐漸變成富含膽固醇酯的成熟HDL。LCAT是HDL代謝的關(guān)鍵酶,當(dāng)LCAT的功能受損時(shí),膽固醇酯的合成會(huì)受到抑制,從而導(dǎo)致高膽固醇血癥：同時(shí),HDL成熟過(guò)程將會(huì)受阻,AS的發(fā)生率將增加。中醫(yī)認(rèn)為血脂異常是內(nèi)因與外因互相作用的結(jié)果,內(nèi)因方面主要是脾失健運(yùn)、肝失疏泄、腎精虧虛,外因包括飲食不節(jié)、情志失調(diào)、勞逸失宜等。病機(jī)方面,認(rèn)為本病本虛標(biāo)實(shí),以正虛為本,濕濁、痰凝、瘀血為標(biāo),脾肝腎三臟功能失調(diào)是產(chǎn)生血脂異常的主要病理基礎(chǔ)。治療方面,辨證論治,主要以疏肝理氣、滋養(yǎng)肝腎、健脾消食,以及活血祛瘀、化痰通絡(luò)為治則。已經(jīng)證實(shí)多種中藥單體成分、單味中藥及中藥復(fù)方能夠調(diào)節(jié)血脂。很多報(bào)道提示中藥能夠提高HDL水平,但是目前對(duì)調(diào)脂中藥通過(guò)調(diào)節(jié)HDL亞型分布來(lái)影響其功能方面研究不足,而且少有從影響HDL抗炎、抗氧化功能出發(fā)研究中藥抗動(dòng)脈粥樣硬化機(jī)制的研究報(bào)道。在前期實(shí)驗(yàn)中我們發(fā)現(xiàn)活血化瘀藥芎芍膠囊抗AS作用確切,AS兔中血脂TC、LDL升高時(shí)伴有HDL升高,考慮HDL具有異質(zhì)性,HDL水平升高并不一定能夠抗AS。在前期研究的基礎(chǔ)上,本次實(shí)驗(yàn)圍繞HDL的亞型、代謝、組分和功能展開(kāi)了進(jìn)一步研究。目的：本研究通過(guò)建立兔動(dòng)脈粥樣硬化模型,從調(diào)節(jié)脂質(zhì)代謝、影響HDL亞型分布及功能的角度探討芎芍膠囊抗AS可能的作用機(jī)制。方法：1.分組和給藥將60只雄性新西蘭兔隨機(jī)分為5組,空白對(duì)照組、模型組、辛伐他汀組、芎芍低劑量組、芎芍高劑量組,各12只。采用單純高脂飼料喂養(yǎng)法建立兔AS模型。給藥方法：①空白對(duì)照組予普通飼料喂養(yǎng)22周；②模型組予高脂飼料喂養(yǎng)14周,接著普通飼料喂養(yǎng)8周；③辛伐他汀組予高脂飼料及辛伐他汀喂養(yǎng)14周,后8周喂養(yǎng)普通飼料及辛伐他汀,辛伐他汀給藥量為2mg/Kg·d；④芎芍低劑量組予高脂飼料及中藥喂養(yǎng)14周,后8周喂普通飼料及中藥,中藥劑量為川芎1.5g/kg·d、赤芍0.75g/kg·d;⑤芎芍高劑量組予高脂飼料及中藥喂養(yǎng)14周,后8周喂普通飼料及中藥,中藥劑量為川芎3.0g/kg·d、赤芍1.5g/kg·d。2.病理組織學(xué)觀察主動(dòng)脈斑塊形成情況22周末麻醉之后處死動(dòng)物,取出胸主動(dòng)脈,肉眼觀察主動(dòng)脈大體標(biāo)本血管壁脂質(zhì)斑塊形成情況。用中性福爾馬林溶液固定,常規(guī)制成組織石蠟切片,蘇木素-伊紅(HE)染色,顯微鏡下觀察其組織病理改變。3.高密度脂蛋白及其他血脂檢測(cè)分別于實(shí)驗(yàn)前、給藥14周、給藥22周3個(gè)時(shí)間點(diǎn)采血,離心后用全自動(dòng)生化分析儀檢測(cè)血清HDL及其組分ApoA-Ⅰ、總膽固醇(TC)、低密度脂蛋白(LDL)、載脂蛋白B(ApoB)、甘油三酯(TG)、極低密度脂蛋白(VLDL)水平。4.高密度脂蛋白亞型檢測(cè)取血清標(biāo)本,采用酶聯(lián)免疫吸附試驗(yàn)法(ELISA)測(cè)定血清中HDL亞型HDL2的水平。5.膽固醇逆轉(zhuǎn)運(yùn)功能檢測(cè)實(shí)驗(yàn)?zāi)┤「谓M織于液氮中凍存。用Trizol法提取肝臟總RNA,實(shí)時(shí)熒光定量聚合酶鏈?zhǔn)椒磻?yīng)(real-time PCR)測(cè)定肝臟ABCAl mRNA、SR-BI mRNA的表達(dá)量。6.高密度脂蛋白抗氧化功能的檢測(cè)采用鄰連茴香胺法測(cè)定血清MPO活性,酶聯(lián)免疫吸附試驗(yàn)法(ELISA)測(cè)定血清PON1活性。7.高密度脂蛋白代謝調(diào)節(jié)采用實(shí)時(shí)熒光定量聚合酶鏈?zhǔn)椒磻?yīng)(real-time PCR)測(cè)定肝臟LCAT mRNA的表達(dá)量。結(jié)果：1.空白對(duì)照組兔主動(dòng)脈管壁表面光滑,內(nèi)皮細(xì)胞連續(xù),未見(jiàn)脂質(zhì)沉積；模型組兔主動(dòng)脈管壁滿布脂質(zhì)斑塊,內(nèi)膜下可見(jiàn)大量堆積的泡沫細(xì)胞,平滑肌層細(xì)胞內(nèi)見(jiàn)大量脂質(zhì)沉積；各給藥組兔主動(dòng)脈管壁表面脂質(zhì)斑塊較模型組減少,顯微鏡下見(jiàn)內(nèi)膜下泡沫細(xì)胞堆積較少。2.給藥及造模14周,除空白對(duì)照組外,各組實(shí)驗(yàn)兔的血清TC、TG、HDL, LDL、VLDL、ApoA-I、ApoB均升高,差異有統(tǒng)計(jì)學(xué)意義(P0.05或P0.01)；給藥22周,除空白對(duì)照組外,各組實(shí)驗(yàn)兔的血清TC、VLDL、ApoA-I較給藥前升高,模型組LDL較給藥前升高,差異有統(tǒng)計(jì)學(xué)意義(P0.05或P0.01)。給藥及造模14周,模型組血清TC、TG、HDL、LDL、VLDL、ApoA-I、ApoB較空白對(duì)照組升高,差異有統(tǒng)計(jì)學(xué)意義(P0.05或P0.01),給藥組與模型組差異無(wú)統(tǒng)計(jì)學(xué)意義。給藥22周,模型組血清TC、LDL、VLDL、ApoA-I較空白對(duì)照組升高,差異有統(tǒng)計(jì)學(xué)意義(P0.01);給藥組血清HDL的變化與模型組相比無(wú)明顯差異；給藥組血清TC、LDL、VLDL較模型組降低,ApoA-I較模型組升高,差異有統(tǒng)計(jì)學(xué)意義(P0.05或P0.01)；其中血清TC、VLDL、ApoA-I在芎芍低、高劑量組與辛伐他汀組之間無(wú)明顯差異。3.給藥22周,模型組血清HDL2較空白對(duì)照組升高,差異有統(tǒng)計(jì)學(xué)意義(P0.05)；辛伐他汀組和芎芍高劑量組血清HDL2的升高程度較模型組更大,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。4.給藥22周末,模型組ABCA1 mRNA表達(dá)量較空白對(duì)照組升高(P0.05)。給藥組ABCA1 mRNA表達(dá)量較模型組明顯升高(P0.01)。模型組SR-BI mRNA表達(dá)量較空白對(duì)照組明顯升高(P0.01)。各給藥組SR-BI mRNA表達(dá)量與模型組相比無(wú)明顯統(tǒng)計(jì)學(xué)差異。5.造模及給藥14周后,模型組血清MPO活性較空白對(duì)照組明顯升高(P0.01),各治療組MPO活性較模型組降低(P0.05)。給藥22周后,模型組MPO活性較空白對(duì)照組升高,差異有統(tǒng)計(jì)學(xué)意義(P0.05)；各給藥組MPO較模型組降低,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。各組實(shí)驗(yàn)兔血清PON1活性改變無(wú)差異(P0.05)。6.給藥22周末,模型組LCAT mRNA表達(dá)量較空白對(duì)照組明顯升高(P0.01)。各給藥組LCAT mRNA表達(dá)量較模型組明顯升高(P0.01)。結(jié)論：1.芎芍膠囊能夠抑制AS兔主動(dòng)脈斑塊形成,減輕脂質(zhì)在血管內(nèi)壁的沉積,減少泡沫細(xì)胞在內(nèi)膜下的聚集。2.芎芍膠囊能夠升高AS兔血清ApoA-I水平,降低TC、LDL、VLDL水平,調(diào)節(jié)脂質(zhì)水平。3.芎芍膠囊能夠升高AS兔血清中HDL2水平,增加HDL成熟亞型顆粒的水平,影響HDL亞型分布。4.芎芍膠囊能夠上調(diào)AS兔肝臟ABCA1 mRNA表達(dá),促進(jìn)肝臟內(nèi)膽固醇代謝,促進(jìn)膽固醇逆轉(zhuǎn)運(yùn),其對(duì)肝臟SR-BI mRNA的調(diào)節(jié)作用不明顯。5.芎芍膠囊能夠降低AS兔血清MPO活性,抑制其氧化HDL中的ApoA-I,保護(hù)HDL抗氧化功能,其對(duì)血清PON1活性作用不明顯。6.芎芍膠囊能夠上調(diào)AS兔肝臟LCAT mRNA表達(dá),促進(jìn)HDL的成熟,影響HDL的功能。7.芎芍膠囊抗動(dòng)脈粥樣硬化的機(jī)制可能與促進(jìn)HDL成熟、增加HDL成熟亞型顆粒水平以及調(diào)節(jié)血脂水平有關(guān)。8.芎芍膠囊抗動(dòng)脈粥樣硬化的機(jī)制可能與增加RCT相關(guān)蛋白基因表達(dá)促進(jìn)RCT,且可能保護(hù)HDL抗氧化功能有關(guān)。
[Abstract]:Atherosclerosis is the pathological basis of various cardiovascular and cerebrovascular diseases. The pathogenesis of atherosclerosis is mainly lipid metabolism, inflammatory reaction, endothelial injury, oxidative stress, etc. High density lipoprotein (HDL) can pass cholesterol reverse transport (Reverse cholesterol transport, RCT), anti-inflammatory, antioxidant, Antithrombotic, anti apoptotic and diastolic blood vessels to protect blood vessels and anti atherosclerotic functions. The latest research has found that the level of HDL alone does not reflect its anti atherosclerotic function, and the function of HDL is closely related to the subtypes of subtypes, metabolism, and components of the.HDL, and the components and functions of the subtypes and functions are now becoming the present anti porridge. .ApoA- I, a hot spot in the study of sample sclerosis, is the main component of the protein and structure of HDL, and is also the main bearer of HDL to complete RCT, anti endothelial cell apoptosis, anti-oxidation, and anti-inflammatory function, the number of.ApoA- I decrease or structural change, the original function of HDL will be weakened or lost, and even the AS action.HDL via pre beta 1-HDL to HDL3 to HDL2. Gradually mature, HDL2, as a large mature HDL subtype, can promote the transport of cholesterol to the liver and the tissue of the synthetic steroid hormone, and the low HDL2 level is negatively related to the risk of coronary heart disease. The adenosine triphosphate binding cassette transporter A1 (ATP-binding cassette transporters A1, ABCA1) can be combined with HDL to promote intracellular cholesterol efflux. The effect of HDL particles formation, participation in RCT, regulating lipid metabolism. In addition, ABCA1 can also inhibit the expression of inflammatory factors and participate in the oxidative stress response in many ways, such as the AS process.B class type I scavenger receptor (Scavenger receptor class B, type I, SR-BI) can selectively absorb cholesterol esters in HDL, transmitted to liver and steroid irrigations The hormone producing tissue, completing RCT, also mediates the cholesterol efflux process of peripheral cells, and participates in the metabolism of many lipoproteins. Myeloperoxidase (MPO) and paroxypase 1 (Paraoxonase 1, PON1) are HDL affecting inflammation, and the associated protein.MPO of oxidative stress can selectively oxidize ApoA- I and weaken or lose the function of HDL. On the contrary, PON1 can directly participate in the hydrolysis of peroxide in lipoprotein to protect HDL from oxidation modification and protect the antioxidant function of HDL. The phosphatidylcholine acyl transferase (Lecithin cholesterol acyltransf erase, LCAT) can esterification the cholesterol, make the cholesterol enter into HDL, and make HDL gradually become rich in the HDL. The mature HDL.LCAT of cholesteryl ester is the key enzyme in the metabolism of HDL. When the function of LCAT is damaged, the synthesis of cholesteryl ester will be inhibited, which leads to hypercholesterolemia. At the same time, the maturation process of HDL will be blocked and the incidence of AS will increase. Loss of health, liver loss, deficiency of kidney essence, and kidney essence deficiency, external causes include diet, emotional disorder, and labor and leisure. On the pathogenesis of the disease, we think that the deficiency of this disease is true, with positive deficiency, wet turbid, phlegm coagulation, blood stasis as the standard, the three dirty function of spleen liver and kidney is the main basis of abnormal blood lipid. Kidney, invigorating the spleen and eliminating food, and activating blood and removing stasis, eliminating phlegm and collaterals as the treatment. It has been proved that many kinds of Chinese medicine monomers, single Chinese medicine and Chinese medicine compound can regulate blood lipid. Many reports suggest that Chinese medicine can improve the level of HDL, but at present, the research on lipid regulating Chinese medicine has not been influenced by the distribution of HDL subtypes to influence its function and has little influence. HDL anti atherosclerotic mechanism of anti atherosclerotic mechanism of traditional Chinese medicine was reported. In the previous experiment, we found that Xiong paehao capsule was effective in anti AS. The serum lipid TC, LDL increased with HDL in AS rabbits, and HDL had heterogeneity, and the elevation of HDL level was not necessarily on the basis of the early study of AS.. In this study, the subtypes, metabolism, components and functions of HDL were further studied. Objective: To explore the possible mechanism of Xiong Shao capsule against AS by setting up the rabbit atherosclerosis model and regulating the lipid metabolism and affecting the distribution and function of the HDL subtype. 1. groups and 60 male New Zealand rabbits were divided into two groups. The machine was divided into 5 groups: blank control group, model group, simvastatin group, Xiong Shao's low dose group, Xiong Shao's high dose group, each 12. The rabbit AS model was established by simple high fat feed feeding method. The method of administration: (1) the blank control group was fed with ordinary feed for 22 weeks; the model group was fed with high fat feed for 14 weeks and then fed with ordinary feed for 8 weeks; 3. The group was fed with high fat diet and simvastatin for 14 weeks, 8 weeks after feeding common feed and simvastatin, the dosage of simvastatin was 2mg/Kg D. 4. The low dose Xiong paehao group was fed with high fat feed and Chinese medicine for 14 weeks, and the ordinary feed and traditional Chinese medicine were fed for 8 weeks. The dose of Chinese medicine was Chuanxiong 1.5g/kg D and Radix Paeoniae 0.75g/kg. D. Feed and traditional Chinese medicine for 14 weeks, 8 weeks after feeding common feed and traditional Chinese medicine, the dose of traditional Chinese medicine was 3.0g/kg D, 1.5g/kg d.2. of Radix Paeoniae Rubra observed the formation of atherosclerotic plaques in the aorta after 22 weekend anesthesia, removed the thoracic aorta, and observed the formation of lipid plaque in the blood tube wall of the main specimens of the aorta. Neutral Faure Marin Young Liquid fixation, routine tissue paraffin section, hematoxylin eosin (HE) staining, microscopically observed histopathological changes of.3. high density lipoprotein and other blood lipids before the experiment, the drug was given 14 weeks, and the drug was given for 22 weeks and 3 time points. After centrifugation, the serum HDL and its component ApoA- I, total cholesterol (TC) were detected by the automatic biochemical analyzer. Low density lipoprotein (LDL), apolipoprotein B (ApoB), triglyceride (TG), extremely low density lipoprotein (VLDL) level.4. high density lipoprotein subtype, serum samples were detected by enzyme linked immunosorbent assay (ELISA), the level of HDL subtype HDL2 in serum was determined by.5. cholesterol reverse transport function test at the end of the experiment, and the liver tissue was frozen in liquid nitrogen. Izol method was used to extract total liver RNA, real-time fluorescent quantitative polymerase chain reaction (real-time PCR) for the determination of liver ABCAl mRNA, the expression of SR-BI mRNA, the antioxidant function of.6. high-density lipoprotein was detected by anisamine method, serum MPO activity was measured by anisamine method. Enzyme linked immunosorbent assay (ELISA) determination of the metabolism of serum PON1 activity high density lipoprotein metabolism The expression of LCAT mRNA in liver was measured by real time fluorescence quantitative polymerase chain reaction (real-time PCR). Results: 1. the aorta wall of rabbits in the blank control group was smooth, endothelial cells were continuous and no lipid deposition was found. The aorta wall of the rabbit model group was covered with lipid plaque, and a large amount of foam cells and smooth muscle layers were visible under the intima. A large amount of lipid deposition was found in the cells, and the lipid plaque on the aortic wall surface of the rabbits was less than that in the model group. Under the microscope, the foam cells of the intima were accumulated less.2. and 14 weeks. Except for the blank control group, the serum TC, TG, HDL, LDL, VLDL, ApoA-I, ApoB of the rabbits in each group were all increased, the difference was statistically significant (P0.05 or P0.01). After 22 weeks of administration, the serum TC, VLDL, and ApoA-I of the rabbits in the experimental group were higher than those in the blank control group. The difference was statistically significant (P0.05 or P0.01) in the model group (P0.05 or P0.01). The serum TC, TG, HDL, LDL, VLDL, ApoA-I, and ApoA-I were higher in the model group than in the blank control group for 14 weeks. There was no significant difference between the drug group and the model group. The serum TC, LDL, VLDL and ApoA-I in the model group were higher than that in the blank control group for 22 weeks. The difference was statistically significant (P0.01). The changes of serum HDL in the administration group were not significantly different from those in the model group; the serum TC, LDL, VLDL were lower in the administration group than the model group, and the ApoA-I was higher than the model group, and the difference was statistically significant. Meaning (P0.05 or P0.01), the serum TC, VLDL and ApoA-I were low in Xiong Shao, there was no significant difference between the high dose group and the simvastatin group for 22 weeks. The serum HDL2 in the model group was higher than that in the blank control group, the difference was statistically significant (P0.05), and the increase of serum HDL2 in the simvastatin group and Xiong Shao high dose group was larger than that in the model group, and the difference was statistically significant. The expression of ABCA1 mRNA in the model group was higher than that in the blank control group (P0.05). The expression of ABCA1 mRNA in the administration group was significantly higher than that in the model group (P0.01). The expression of SR-BI mRNA in the model group was significantly higher than that in the blank control group (P0.01). There was no significant difference in the expression of the SR-BI mRNA expression in the group of the drug groups compared with the model group (P0.05). The expression of ABCA1 mRNA in the model group was significantly higher than that in the model group (P0.01). After 14 weeks of administration, the activity of serum MPO in the model group was significantly higher than that in the blank control group (P0.01). The activity of MPO in each treatment group was lower than that in the model group (P0.05). After 22 weeks of administration, the activity of MPO in the model group was higher than that in the blank control group (P0.05), and the MPO in each group was lower than that in the model group (P0.05). The difference was statistically significant (P0.05). The changes of PON1 activity in rabbit serum were no difference (P0.05).6. administration at the end of 22 weeks. The expression of LCAT mRNA in the model group was significantly higher than that in the blank control group (P0.01). The expression of LCAT mRNA in each group was significantly higher than that in the model group (P0.01). Conclusion: 1. Xiong Shao Shao capsule can inhibit the formation of the aortic plaque in the aorta of AS rabbits, reduce the deposition of lipid on the inner wall of the blood vessels and reduce the bubbles. .2. Xiong Shao capsule can increase the level of ApoA-I in serum of AS rabbit and reduce the level of TC, LDL, VLDL. The regulation of lipid level.3. xiushao capsule can increase the level of HDL2 in the serum of AS rabbit, increase the level of HDL mature subtype, and influence the HDL subtype distribution of.4. Xiong Shao capsule to increase the expression of liver and promote the liver. Intracellular cholesterol metabolism, promote cholesterol reverse transport, its regulating effect on liver SR-BI mRNA is not obvious,.5. Xiong Shao capsule can reduce the activity of MPO in serum of AS rabbit, inhibit the ApoA-I in HDL, protect the antioxidant function of HDL, and its effect on serum PON1 activity is not obvious,.6. Xiong Shao capsule can up regulate AS rabbit liver LCAT The anti atherosclerosis mechanism of Xiong Shao capsule, the function of HDL, may be related to the mechanism of promoting the maturation of HDL, increasing the level of HDL mature subtype particles and regulating the level of blood lipid. The mechanism of anti atherosclerosis of Xiong paehao capsule of.8. may be related to increasing the expression of RCT related protein gene expression to promote RCT, and may protect the antioxidant function of HDL.
【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R285

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