黄芪甲苷对慢性心衰大鼠的心脏保护作用及机制研究

发布时间：2018-05-15 16:36

  本文选题：黄芪甲苷 + 慢性心衰　； 参考：《山东大学》2017年硕士论文

【摘要】：目的采用腹主动脉缩窄法(AAC)建立慢性心衰(CHF)大鼠模型,研究黄芪甲苷对CHF大鼠的心脏保护作用,并从心肌能量代谢角度探讨其可能机制。方法对120只基线情况相同的SD大鼠中的95只采用AAC法建立CHF模型,对另外25只SD大鼠采用与AAC法相同但不结扎腹主动脉的方式建立假手术组。术后8周通过心脏超声(UCG)及相关生化指标评价模型建立情况,将建模成功的大鼠随机分为盐酸贝那普利组、模型组、低剂量黄芪甲苷组、高剂量黄芪甲苷组,每组22只。盐酸贝那普利组大鼠给予10mg.kg-1.d1的盐酸贝那普利灌胃,低剂量及高剂量黄芪甲苷组大鼠给予25 mg.kg-1.d-1及50 mg.kg-1.d-1的黄芪甲苷灌胃,假手术组及模型组给予1%羧甲基纤维素灌胃处理。连续干预8周后通过UCG检测各组大鼠心脏相关结构及功能指标,通过左室插管测定各组大鼠血流动力学变化,留取血液标本后通过腹腔注射大剂量戊巴比妥钠(20 mg.kg-1)处死大鼠,留取心脏,用乳酸林格氏液洗净血液后滤纸吸干多余液体,称取心脏全心重量及左心室重量。部分左心室于福尔马林中固定,制作病理切片观察心肌形态学变化;部分左心室置于-80℃冰箱中保存,通过蛋白免疫印迹(western-blot)及实时定量聚合酶链式反应(RT-qPCR)检测过氧化物酶体增殖物激活受体a(PPARa)、中链脂酰辅酶A脱氢酶(MCAD)、肌型肉碱棕榈酰转移酶-1(CPT1B)蛋白及mRNA的表达情况。所有数据以均数±标准差表示,通过单因素方差分析明确各组数据有无统计学差异,有差异时用SNK-q检验进行多重比较,明确差异存在于哪两个组,以P0.05作为差异有统计学意义的标准。结果(1)与假手术组相比,模型组大鼠PPARa、MCAD、CPT1B表达及左室射血分数(LVEF)下降,左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室后壁厚度(LVPWD)、游离脂肪酸(FFA)水平升高;(2)与模型组相比,黄芪甲苷组大鼠PPARa、MCAD、CPT1B表达及左室射血分数(LVEF)升高,LVEDD、LVESD、LVPWD、FFA水平下降;(3)与盐酸贝那普利组相比,低剂量黄芪甲苷组PPARa、MCAD、CPT1B 表达及 LVEF 下降,LVEDP、LVESP、LVPWD水平升高,高剂量黄芪甲苷组大鼠上述指标则未见明显差异。结论(1)CHF大鼠的心脏可以出现胶原纤维增生、心肌细胞肥大、心肌细胞排列紊乱等,其机制与心肌细胞能量代谢异常有关。(2)黄芪甲苷可以抑制CHF大鼠心室重构、改善心功能、抑制心肌纤维化,其作用强度与剂量有关;(3)黄芪甲苷对CHF大鼠的心脏保护作用与其上调PPARa、MCAD、CPT1B的蛋白及mRNA表达、改善心肌对脂肪酸的利用,从而改善心肌能量代谢有关。(4)高剂量黄芪甲苷对CHF大鼠的心脏保护作用与盐酸贝那普利在相关指标上效果相当。
[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，

本文编号：1893100