本文選題：黃芪甲苷 + 慢性心衰　； 參考：《山東大學(xué)》2017年碩士論文

【摘要】：目的采用腹主動脈縮窄法(AAC)建立慢性心衰(CHF)大鼠模型,研究黃芪甲苷對CHF大鼠的心臟保護(hù)作用,并從心肌能量代謝角度探討其可能機(jī)制。方法對120只基線情況相同的SD大鼠中的95只采用AAC法建立CHF模型,對另外25只SD大鼠采用與AAC法相同但不結(jié)扎腹主動脈的方式建立假手術(shù)組。術(shù)后8周通過心臟超聲(UCG)及相關(guān)生化指標(biāo)評價模型建立情況,將建模成功的大鼠隨機(jī)分為鹽酸貝那普利組、模型組、低劑量黃芪甲苷組、高劑量黃芪甲苷組,每組22只。鹽酸貝那普利組大鼠給予10mg.kg-1.d1的鹽酸貝那普利灌胃,低劑量及高劑量黃芪甲苷組大鼠給予25 mg.kg-1.d-1及50 mg.kg-1.d-1的黃芪甲苷灌胃,假手術(shù)組及模型組給予1%羧甲基纖維素灌胃處理。連續(xù)干預(yù)8周后通過UCG檢測各組大鼠心臟相關(guān)結(jié)構(gòu)及功能指標(biāo),通過左室插管測定各組大鼠血流動力學(xué)變化,留取血液標(biāo)本后通過腹腔注射大劑量戊巴比妥鈉(20 mg.kg-1)處死大鼠,留取心臟,用乳酸林格氏液洗凈血液后濾紙吸干多余液體,稱取心臟全心重量及左心室重量。部分左心室于福爾馬林中固定,制作病理切片觀察心肌形態(tài)學(xué)變化;部分左心室置于-80℃冰箱中保存,通過蛋白免疫印跡(western-blot)及實(shí)時定量聚合酶鏈?zhǔn)椒磻?yīng)(RT-qPCR)檢測過氧化物酶體增殖物激活受體a(PPARa)、中鏈脂酰輔酶A脫氫酶(MCAD)、肌型肉堿棕櫚酰轉(zhuǎn)移酶-1(CPT1B)蛋白及mRNA的表達(dá)情況。所有數(shù)據(jù)以均數(shù)±標(biāo)準(zhǔn)差表示,通過單因素方差分析明確各組數(shù)據(jù)有無統(tǒng)計(jì)學(xué)差異,有差異時用SNK-q檢驗(yàn)進(jìn)行多重比較,明確差異存在于哪兩個組,以P0.05作為差異有統(tǒng)計(jì)學(xué)意義的標(biāo)準(zhǔn)。結(jié)果(1)與假手術(shù)組相比,模型組大鼠PPARa、MCAD、CPT1B表達(dá)及左室射血分?jǐn)?shù)(LVEF)下降,左室舒張末期內(nèi)徑(LVEDD)、左室收縮末期內(nèi)徑(LVESD)、左室后壁厚度(LVPWD)、游離脂肪酸(FFA)水平升高;(2)與模型組相比,黃芪甲苷組大鼠PPARa、MCAD、CPT1B表達(dá)及左室射血分?jǐn)?shù)(LVEF)升高,LVEDD、LVESD、LVPWD、FFA水平下降;(3)與鹽酸貝那普利組相比,低劑量黃芪甲苷組PPARa、MCAD、CPT1B 表達(dá)及 LVEF 下降,LVEDP、LVESP、LVPWD水平升高,高劑量黃芪甲苷組大鼠上述指標(biāo)則未見明顯差異。結(jié)論(1)CHF大鼠的心臟可以出現(xiàn)膠原纖維增生、心肌細(xì)胞肥大、心肌細(xì)胞排列紊亂等,其機(jī)制與心肌細(xì)胞能量代謝異常有關(guān)。(2)黃芪甲苷可以抑制CHF大鼠心室重構(gòu)、改善心功能、抑制心肌纖維化,其作用強(qiáng)度與劑量有關(guān);(3)黃芪甲苷對CHF大鼠的心臟保護(hù)作用與其上調(diào)PPARa、MCAD、CPT1B的蛋白及mRNA表達(dá)、改善心肌對脂肪酸的利用,從而改善心肌能量代謝有關(guān)。(4)高劑量黃芪甲苷對CHF大鼠的心臟保護(hù)作用與鹽酸貝那普利在相關(guān)指標(biāo)上效果相當(dāng)。
[Abstract]:Objective to establish a rat model of chronic heart failure (CHF) by abdominal aortic coarctation (AAC), to study the cardioprotective effect of astragaloside on CHF rats, and to explore its possible mechanism from the point of view of myocardial energy metabolism. Methods CHF model was established by AAC in 95 of 120 SD rats with the same baseline. The sham operation group was established in 25 SD rats using the same method as AAC without ligation of abdominal aorta. At 8 weeks after operation, the model was established by echocardiography (UCG) and related biochemical indexes. The rats were randomly divided into benazepril hydrochloride group, model group, low dose astragaloside group and high dose astragaloside group with 22 rats in each group. The rats in benazepril group were given benazepril hydrochloride of 10mg.kg-1.d1, the rats in low and high dose group were given 25 mg.kg-1.d-1 and 50 mg.kg-1.d-1 of astragaloside, and the sham operation group and model group were given 1% carboxymethyl cellulose. After 8 weeks of continuous intervention, the cardiac structure and function were measured by UCG, hemodynamic changes were measured by left ventricular catheterization, and the rats were killed by intraperitoneal injection of high dose pentobarbital sodium (20 mg 路kg ~ (-1). Retain the heart, wash the blood with Ringer's lactate liquid, then drain the excess fluid with filter paper, and weigh the heart weight and left ventricular weight. Some left ventricle were fixed in formalin, pathological sections were made to observe the morphologic changes of myocardium, and some left ventricle were stored in -80 鈩，

本文編號：1893100