本文關(guān)鍵詞： 隔藥餅灸 高脂血癥 動(dòng)脈粥樣硬化 膽固醇逆轉(zhuǎn)運(yùn) 炎癥因子　出處：《湖南中醫(yī)藥大學(xué)》2016年博士論文　論文類型：學(xué)位論文

【摘要】：目的:1、觀察隔藥餅灸對(duì)動(dòng)脈粥樣硬化兔血脂代謝變化、組織結(jié)構(gòu)變化和血清相關(guān)炎性因子的影響;2、觀察隔藥餅灸對(duì)動(dòng)脈粥樣硬化兔膽固醇逆轉(zhuǎn)運(yùn)SR-B1介導(dǎo)途徑中PPARγ、SR-B1表達(dá)的影響,探討隔藥餅灸抗AS的作用機(jī)制。方法:健康純種雄性新西蘭大耳白兔40只隨機(jī)分為5組:空白對(duì)照組,模型組,隔藥餅灸組,直接灸組,辛伐他汀組。采用高脂飼料喂養(yǎng)方式制備高脂血癥合并AS兔模型,分別給予不同干預(yù)手段進(jìn)行治療,干預(yù)結(jié)束后,禁食,經(jīng)耳緣靜脈麻醉后采集血液樣本,處死動(dòng)物,取主動(dòng)脈及肝臟樣本。各組兔主動(dòng)脈、肝臟標(biāo)本HE染色,觀察組織變化情況;酶法測(cè)定血清中總膽固醇(TC)、甘油三酯(TG)、低密度脂蛋白膽固醇(LDL-C)、高密度脂蛋白膽固醇(HDL-C)水平,測(cè)定膽固醇含量;酶聯(lián)免疫吸附法(ELISA)測(cè)定血清中腫瘤壞死因子α(TNF-a)、干擾素γ(IFN-γ),白介素6(IL-6)白介素10(IL-10)水平;蛋白印跡法(WB)測(cè)定肝臟PPARγ、SR-B1蛋白表達(dá)量;實(shí)時(shí)定量聚合酵鏈?zhǔn)椒磻?yīng)(real-time邋PCR)測(cè)定肝臟PPARγ、SR-B1 mRNA表達(dá)量。結(jié)果:1、正常組主動(dòng)脈血管壁內(nèi)膜表面光滑,各層結(jié)構(gòu)清晰,內(nèi)皮細(xì)胞完整連續(xù),平滑肌細(xì)胞排列整齊緊密有序,無(wú)脂質(zhì)、斑塊等沉積;模型組主動(dòng)脈血管壁明顯增厚,內(nèi)皮層脫落,管壁滿布脂質(zhì)、斑塊,大量泡沫細(xì)胞出現(xiàn);隔藥餅灸組和直接灸組內(nèi)膜輕度增厚,平滑肌細(xì)胞厚度均勻、排列整齊,少見(jiàn)泡沫細(xì)胞;辛伐他汀組內(nèi)膜增厚,各層結(jié)構(gòu)相比于模型組清晰,有泡沫細(xì)胞形成,內(nèi)膜下少量脂質(zhì)沉積,未見(jiàn)明顯斑塊。正常組肝組織結(jié)構(gòu)明顯,肝細(xì)胞核顯示清楚,肝竇空虛、無(wú)瘀血,無(wú)脂質(zhì)變性,排列規(guī)整,呈多邊形分布,胞漿均勻;模型組肝組織結(jié)構(gòu)不清晰,部分肝竇變窄或缺失,內(nèi)皮細(xì)胞不明顯,肝細(xì)胞腫脹、胞漿透明,部分肝細(xì)胞呈脂肪變性,部分出現(xiàn)脂滴融合,脂肪空泡彌漫充布,間質(zhì)組織有淋巴細(xì)胞和漿細(xì)胞的浸潤(rùn);隔藥灸組和直接灸組肝臟組織結(jié)構(gòu)比較清晰,肝細(xì)胞輕度脂肪變性,肝臟組織的脂滴沉積減少,輕度炎性反應(yīng);辛伐他汀組肝細(xì)胞脂肪變性程度較模型組減輕,少數(shù)有脂滴空泡,肝組織結(jié)構(gòu)有改變,少量肝細(xì)胞呈現(xiàn)水樣變性,大部分肝細(xì)胞核位置未發(fā)生改變,形態(tài)相對(duì)正常。2、與正常組比較,模型組兔的血清TC、TG、LDL-C水平較高,差異有統(tǒng)計(jì)學(xué)意義(p0.01);模型組兔的血清hdl-c水平較低,差異有統(tǒng)計(jì)學(xué)意義(p0.01)。與模型組比較,隔藥餅灸組、直接灸組、辛伐他汀組血清tc、tg、ldl-c降低明顯,hdl-c水平升高,差異有統(tǒng)計(jì)學(xué)意義。與正常組比較,模型組主動(dòng)脈、肝組織、脂肪組織的膽固醇含量較高,差異有統(tǒng)計(jì)學(xué)意義(p0.01)。與模型組比較,隔藥餅灸組、直接灸組、辛伐他汀組主動(dòng)脈、肝組織、脂肪組織的膽固醇含量明顯降低,差異有統(tǒng)計(jì)學(xué)意義(p0.01)。3、與正常組比較,模型組、直接灸組、辛伐他汀組血清il-6、tnf-α、ifnγ表達(dá)升高,有顯著性差異(p0.01或p0.05),隔藥灸組與正常組比較,il-6、ifnγ無(wú)顯著性差異,tnf-α表達(dá)升高與正常組有顯著差異;與模型組相比,隔藥灸組、直接灸組、辛伐他汀組血清il-6、tnf-α、ifnγ表達(dá)均有明顯降低,差異有統(tǒng)計(jì)學(xué)意義(p0.01或p0.05)。與正常組比較,模型組、辛伐他汀組血清il-10表達(dá)明顯減少,差異有統(tǒng)計(jì)學(xué)意義(p0.05);與模型組相比,隔藥灸組、直接灸組、辛伐他汀組血清il-10表達(dá)均有明顯升高,差異有統(tǒng)計(jì)學(xué)意義(p0.01或p0.05)。4、與正常組比較,模型組pparγ、sr-b1蛋白表達(dá)降低,差異有統(tǒng)計(jì)學(xué)意義(p0.01或p0.05),隔藥灸組肝臟pparγ、sr-b1蛋白表達(dá)較高,差異有統(tǒng)計(jì)學(xué)意義(p0.01或p0.05),直接灸組兔肝臟pparγ蛋白表達(dá)較高,差異有統(tǒng)計(jì)學(xué)意義(p0.01或p0.05),sr-b1蛋白表達(dá)與正常組比較無(wú)統(tǒng)計(jì)學(xué)差異;與模型組相比較,隔藥灸組、直接灸組、辛伐他汀組肝臟的pparγ、sr-b1蛋白表達(dá)均呈升高趨勢(shì),差異有統(tǒng)計(jì)學(xué)意義(p0.01或p0.05);與隔藥灸組相比較,直接灸組、辛伐他汀組肝臟的pparγ、sr-b1蛋白表達(dá)均呈降低趨勢(shì),差異有統(tǒng)計(jì)學(xué)意義(p0.01或p0.05)。與正常組比較,模型組肝臟pparγ、sr-b1mrna表達(dá)降低,差異有統(tǒng)計(jì)學(xué)意義(p0.05),隔藥灸組、直接灸組肝臟pparγ、sr-b1mrna表達(dá)較高,差異有統(tǒng)計(jì)學(xué)意義(p0.05),辛伐他汀組肝臟pparγmrna表達(dá)較高,差異有統(tǒng)計(jì)學(xué)意義(p0.05),sr-b1mrna表達(dá)與正常組比較無(wú)統(tǒng)計(jì)學(xué)差異;與模型組相比較,隔藥灸組、直接灸組、辛伐他汀組肝臟的pparγ、sr-b1mrna表達(dá)均升高,差異有統(tǒng)計(jì)學(xué)意義(p0.01或p0.05);與隔藥灸組相比較,直接灸組、辛伐他汀組肝臟的pparγ、sr-b1mrna表達(dá)均呈降低趨勢(shì),差異有統(tǒng)計(jì)學(xué)意義(p0.01或p0.05)。結(jié)論:1、隔藥餅灸對(duì)動(dòng)脈粥樣硬化兔血脂代謝變化具有良性調(diào)節(jié)作用,對(duì)動(dòng)脈內(nèi)膜、肝臟等組織病理變化有修復(fù)作用。2、隔藥餅灸抗動(dòng)脈粥樣硬化作用可能與其對(duì)動(dòng)脈粥樣硬化兔血清相關(guān)炎性因子的影響有關(guān)。3、隔藥餅灸影響膽固醇逆轉(zhuǎn)運(yùn)SR-B1介導(dǎo)途徑中PPARγ、SR-B1蛋白及基因表達(dá),激活PPARγ,誘導(dǎo)SR-B1的表達(dá),可以促進(jìn)膽固醇逆轉(zhuǎn)運(yùn),抑制或減緩動(dòng)脈粥樣硬化,可能是隔藥餅灸抗動(dòng)脈粥樣硬化的作用機(jī)制之一。
[Abstract]:Objective: To observe the change of blood lipid metabolism in 1 rabbits with atherosclerosis moxibustion effect, the changes of organizational structure and the related serum inflammatory factors; 2, the observation of cake separated moxibustion on cholesterol reverse transport of atherosclerotic rabbit SR-B1 mediated pathway in PPAR gamma, SR-B1 expression, and explore mechanisms of moxibustion on anti AS methods: male purebred New Zealand 40 rabbits were randomly divided into 5 groups: control group, model group, moxibustion group, direct moxibustion group and simvastatin group. The rabbit model of hyperlipidemia and AS by feeding high fat diet, respectively given different interventions for treatment, intervention after fasting, intravenously after anesthesia, blood samples were taken, animal, aorta and liver samples. The Rabbits Aorta, liver specimens HE staining, observe the changes of tissue; Determination of total serum bile cholesterol enzyme (TC), triglyceride (TG), Low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) levels, determination of cholesterol content; enzyme linked immunosorbent assay (ELISA) determination of tumor necrosis factor alpha in serum (TNF-a) and interferon gamma (IFN- gamma), interleukin 6 (IL-6) and interleukin 10 (IL-10) protein level; Western blot (WB) were detected by PPAR gamma, SR-B1 protein expression; real-time quantitative polymerase chain reaction (real-time cream yeast PCR) determination of liver PPAR SR-B1 gamma, the expression of mRNA. Results: 1, normal aortic wall intimal smooth surface, each layer of the structure is clear, endothelial cells complete and continuous, smooth muscle cells arranged in neat rows closely, no lipid plaque deposition; model group aortic wall thickening, endothelial layer off, the wall covered with lipid plaque, a large number of foam cells; moxibustion group and direct moxibustion group in membrane mild thickening, smooth muscle cells arranged in neat, uniform thickness, rare bubble Foam cell; simvastatin group intimal thickening, compared the structure of each layer in the model group, with the formation of foam cells and a small amount of lipid deposition under intima, no obvious plaque. Normal liver tissue structure significantly, liver nuclei showed clear liver sinus empty, no blood, no change of lipid, ordered, polygonal cell distribution. Pulp evenly; model group liver tissue structure is clear, part of the liver sinus narrowing or lack of endothelial cells is not obvious, liver cell swelling, clear cytoplasm, part of the liver cells showed fatty degeneration, some lipid droplets fused, fat vacuoles diffuse filling cloth, interstitial tissue infiltration of lymphocytes and plasma cells; isolation medicine moxibustion group and liver tissue in direct moxibustion group structure is relatively clear, mild liver cell fatty degeneration, lipid deposition in liver tissue decreased, mild inflammatory reaction; simvastatin group the degree of liver steatosis reduced compared with model group, there are a few lipid droplet vacuoles, The liver structure changes, a small amount of liver cells showed hydropic degeneration, most liver nuclei did not change the position, form relatively normal.2, compared with the normal group, serum TC, TG in the model group, the LDL-C level is higher, the difference was statistically significant (P0.01); the serum level of HDL-C in the model group was statistically lower significant differences (P0.01). Compared with the model group, moxibustion group, direct moxibustion group, simvastatin group, serum TC, TG, LDL-C decreased, HDL-C level increased, the difference was statistically significant. Compared with the normal group, model group, liver aorta, cholesterol content of adipose tissue is higher, the difference was statistically significant (P0.01). Compared with the model group, moxibustion group, direct moxibustion group, simvastatin group, liver aorta, cholesterol content of adipose tissue decreased significantly, the difference was statistically significant (.3, P0.01) compared with the normal group, model group, direct moxibustion group, Essien In the statin group serum IL-6, tnf- alpha, IFN expression increased significantly (P0.01 or P0.05), moxibustion group compared with normal group, no significant difference in IL-6, IFN gamma, tnf- expression increased significantly compared with normal group; compared with the model group, moxibustion group, direct moxibustion group, simvastatin group, serum IL-6, tnf- alpha, IFN expression decreased significantly, the difference was statistically significant (P0.01 or P0.05). Compared with the normal group, model group, simvastatin group serum IL-10 expression was significantly reduced, the difference was statistically significant (P0.05); compared with the model group, moxibustion group, direct moxibustion the expression of serum IL-10 group, simvastatin group were significantly increased, the difference was statistically significant (P0.01 or P0.05).4, compared with the normal group, model group, PPAR gamma, SR-B1 protein expression decreased, the difference was statistically significant (P0.01 or P0.05), moxibustion group liver PPAR gamma, SR-B1 protein expression is higher, the difference was significant Yi (P0.01 or P0.05), direct moxibustion group of rabbit liver PPAR gamma protein expression was higher, the difference was statistically significant (P0.01 or P0.05), the expression of SR-B1 protein showed no significant difference compared with the normal group; compared with the model group, moxibustion group, direct moxibustion group, simvastatin group PPAR gamma liver, the expression of SR-B1 protein increased, the difference was statistically significant (P0.01 or P0.05); compared with moxibustion group, direct moxibustion group, simvastatin group PPAR gamma liver, SR-B1 protein expression were decreased, the difference was statistically significant (P0.01 or P0.05). Compared with the normal group, model group, liver PPAR, sr-b1mrna the expression is reduced, the difference was statistically significant (P0.05), moxibustion group, direct moxibustion group liver PPAR, sr-b1mrna expression was higher, the difference was statistically significant (P0.05), simvastatin group liver PPAR gamma mRNA expression was higher, the difference was statistically significant (P0.05), and the expression of sr-b1mrna in normal group There was no significant difference; compared with the model group, moxibustion group, direct moxibustion group, simvastatin group PPAR gamma liver, the expression of sr-b1mrna was increased, the difference was statistically significant (P0.01 or P0.05); compared with moxibustion group, direct moxibustion group, simvastatin group liver PPAR gamma, sr-b1mrna expression decreased, the difference was statistically significant (P0.01 or P0.05). Conclusion: 1. Moxibustion has a good regulating effect on blood lipid metabolism in rabbits with atherosclerosis changes on arterial intima, the liver tissue pathological changes of repair.2, medicine separated moxibustion anti atherosclerosis effect may be related to atherosclerosis in rabbit serum inflammatory factors related to.3, moxibustion effect of reverse cholesterol transport mediated by SR-B1 pathway in PPAR gamma, SR-B1 protein expression and gene activation, PPAR gamma, induce the expression of SR-B1, can promote the reverse cholesterol transport, inhibit or slow down Atherosclerosis may be one of the mechanisms of anti atherosclerotic action of cake separated moxibustion.

【學(xué)位授予單位】：湖南中醫(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)】：R245

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本文編號(hào)：1478306