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山楂叶总黄酮对急性心肌梗死大鼠心功能的影响及其机制探讨 被引量:10

Beneficial effects and related mechanism of hawthorn leaves flavonoids on cardiac function in rats with acute myocardial infarction
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摘要 目的探讨山楂叶总黄酮(FHL)对急性心肌梗死(AMI)大鼠心功能的影响及其作用机制。方法SPF级雄性Sprague-Dawley大鼠60只,9周龄,体重300-350 g,采用随机数字表法选取10只作为假手术组,余50只用于建立AMI模型。采用冠状动脉结扎法建立大鼠AMI模型,其中36只建模成功,随机数字表法将其分为AMI组及FHL低、中、高剂量组(每组n=9),按10 ml/kg体重分别腹腔注射生理盐水及浓度为0.3、0.6、1.2 mg/ml的FHL溶液。假手术组仅穿线不结扎,按10 ml/kg体重给予等量生理盐水。给药干预均为1次/d,连续4周。超声心动图检测各组大鼠左心室舒张末期内径(LVEDD)、左心室舒张末期前壁厚度(LAWD)、左心室射血分数(LVEF)及左心室舒张末压(LVEDP)。然后处死大鼠,取左心室前壁组织制作切片,常规苏木精-伊红(HE)染色观察大鼠心肌组织病理学改变。另取切片进行原位末端转移酶标记法(TUNEL)染色,计算心肌细胞凋亡率。分别采用实时荧光定量PCR(RT-qPCR)和Western blot法检测大鼠心肌组织中磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(Akt)、糖原合成酶激酶3(GSK3β)、细胞周期蛋白D1(cyclin D1)mRNA和蛋白的相对表达水平及磷酸化Akt(p-Akt)、磷酸化GSK3β(p-GSK3β)蛋白的相对表达水平。结果与假手术组比较,AMI组及FHL低、中、高剂量组大鼠LVEDD、LVEDP均较大,LAWD、LVEF均较小(P均<0.05)。与AMI组比较,FHL低、中、高剂量组大鼠LVEDD、LVEDP均较小,LAWD、LVEF均较大(P均<0.05),且随FHL剂量增加LVEDD和LVEDP减小,LAWD和LVEF增大(P均<0.05)。FHL低、中剂量组大鼠的LVEDD和LAWD差异无统计学意义(P均>0.05)。HE染色结果显示,假手术组大鼠心肌组织结构正常,AMI组大鼠梗死区可见坏死心肌组织,心肌纤维排列紊乱,心肌间质大量炎性细胞浸润,FHL低、中、高剂量组大鼠心肌损伤较AMI组轻,心肌纤维排列整齐,但仍有部分断裂及少量炎性细胞浸润,梗死区有散在的岛状� Objective To explore the effect and related regulatory mechanism of hawthorn leaf flavonoids(FHL)on cardiac function in rats with acute myocardial infarction(AMI).Methods Sixty SPF male Sprague-Dawley rats(9-week-old,weighing 300-350 g)were used in this study.Ten rats were assigned to sham operation group,and the remaining 50 rats were used to establish the AMI model with coronary artery ligation method,AMI was successfully established in 36 rats.AMI rats were randomly divided into AMI group and FHL low-,medium-,and high-dose groups(n=9 for each group).Rats received intraperitoneal injection(10 ml·kg-1·day-1)with physiological saline and FHL solution with concentrations of 0.3,0.6,and 1.2 mg/ml,respectively for 4 consecutive weeks.Echocardiography was performed at the end of experiments.Left ventricular end diastolic diameter(LVEDD),left ventricular end diastolic anterior wall thickness(LAWD),left ventricular ejection fraction(LVEF)and left ventricular end diastolic pressure(LVEDP)were measured.Then the rats were sacrificed under deep anesthesia,and the left ventricular anterior wall tissue was used for pathological examinations by hematoxylin-eosin(HE)staining.Other myocardial tissue was used for in situ terminal transferase labeling(TUNEL)staining,and the apoptosis rate of cardiomyocytes was calculated.The myocardial cell apoptosis rate,the mRNA,and protein expressions of phosphatidylinositol 3β-kinase(PI3K),protein kinase B(Akt),glycogen synthetase kinase-3(GSK3β),cyclin D1 and the protein expressions of p-Akt and p-GSK3βwere detected by real-time fluorescent quantitative PCR(RT-qPCR)and Western blot respectively.Results Compared with sham operation group,the LVEDD and LVEDP of the rats in AMI group and FHL low-,medium-and high-dose groups were increased,and the LAWD and LVEF were reduced(all P<0.05).Compared with AMI group,LVEDD and LVEDP were reduced,and LAWD and LVEF were increased in FHL low-,medium-and high-dose groups(all P<0.05).LVEDD and LVEDP decreased,and LAWD and LVEF increased in proportion to
作者 张晓慧 刘建东 于峰伟 王东伟 Zhang Xiaohui;Liu Jiandong;Yu Fengwei;Wang Dongwei(Department 3 of Cardiovascular Medicine,Zhumadian Central Hospital,Zhumadian 463000,China)
出处 《中华心血管病杂志》 CAS CSCD 北大核心 2021年第7期701-707,共7页 Chinese Journal of Cardiology
基金 2018年度河南省医学科技攻关计划(2018010047)。
关键词 心肌梗死 心脏功能 山楂叶总黄酮 Myocardial infarction Heart function Hawthorn leaves total flavonoids
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