目的 探讨黄芪甲苷对慢性心力衰竭(CHF)大鼠心肌肥厚的影响,及对磷酸肌醇-3-激酶/蛋白激酶B/糖原合成酶激酶-3β(PI3K/Akt/GSK3β)信号通路的调节作用.方法 用冠状动脉前降支结扎法建立CHF大鼠模型,并随机分为模型组、对照组和低、中、高剂量实验组,每组8只;另取8只大鼠仅挂线,不结扎,作为空白组.低、中、高剂量实验组分别按照5 mL·kg-1的剂量灌胃给予20、40、80 mg·mL-1黄芪甲苷溶液;对照组按照5 mL·kg-1的剂量灌胃给予1.50 mg·kg-1赖诺普利溶液;空白组和模型组均灌胃给予等体积的0.9％NaCl.6组大鼠每天给药1次,连续给药8周.用超声心动图检测大鼠心脏功能,用小麦胚凝集素染色法观察心肌细胞横截面积,用蛋白质印迹法检测PI3K、Akt和GSK3β蛋白的表达水平.结果 高剂量实验组、对照组、模型组和空白组的左心室射血分数分别为(66.27±5.18)％、(67.75±4.98)％、(46.67±3.68)％和(81.65±6.46)％,左心室舒张末期内径分别为(0.53±0.05)、(0.55±0.05)、(0.45±0.02)和(0.57±0.05)mm,心肌细胞横截面积分别为(1.97±0.13)、(1.61±0.18)、(3.56±0.59)和(1.00±0.04)mm,磷酸化 PI3K 蛋白相对表达水平分别为 0.45±0.04、0.71±0.07、0.11±0.02 和0.85±0.06,磷酸化 Akt 蛋白相对表达水平分别为 0.43±0.05、0.75±0.06、0.10±0.03 和 0.82±0.06,磷酸化GSK3β蛋白相对表达水平分别为0.47±0.04、0.85±0.05、0.12±0.04和0.89±0.08.高剂量实验组和对照组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P＜0.05).结论 黄芪甲苷可改善CHF大鼠心功能障碍、抑制心肌肥厚,可能与调节PI3K/Akt/GSK3β信号通路有关.
Objective To investigate the effects of astragaloside Ⅳ on cardiac hypertrophy in chronic heart failure(CHF)rats,and the regulation of phosphoinositol-3-kinase/protein kinase B/glycogen synthase kinase 3 β(PI3K/Akt/GSK3β)signaling pathway.Methods CHF rat model was established by anterior descending coronary artery ligation,and randomly divided into model group,control group and experimental-L,-M,-H groups,with 8 rats in each group.Another 8 rats were hooked up without ligature as blank group.The experimental-L,-M,-H groups were given 20,40 and 80 mg·mL-1 astragaloside solution according to the dose of 5 mL·kg-1.The control group was given 1.50 mg·kg-1 lisinopril solution at a dose of 5 mL·kg-1.Both blank group and model group were given equal volume of 0.9％NaCl.Six groups of rats were given the drug once a day for 8 weeks by intragastric administration.The cardiac function of rats was measured by echocardiography,the cross-sectional area of cardiomyocytes was observed by wheat embryo lectin staining,and the expression levels of PI3K,Akt and GSK3β were detected by Western blot.Results The left ventricular ejection fraction of experimental-H,control,model and blank groups were(66.27±5.18)％,(67.75±4.98)％,(46.67±3.68)％and(81.65±6.46)％;left ventricular end-diastolic diameter was(0.53±0.05),(0.55±0.05),(0.45±0.02)and(0.57±0.05)mm;the cross-sectional areas of cardiomyocytes were(1.97±0.13),(1.61±0.18),(3.56±0.59)and(1.00±0.04)mm;the relative expression levels of phosphorylated PI3K protein were 0.45±0.04,0.71±0.07,0.11±0.02 and 0.85±0.06;the relative expression levels of phosphorylated Akt protein were 0.43±0.05,0.75±0.06,0.10±0.03 and 0.82±0.06;the relative expression levels of phosphorylated GSK3 β protein were 0.47±0.04,0.85±0.05,0.12±0.04 and 0.89±0.08,respectively.The above indexes of experimental-H group and control group were significantly different from those of model group(all P＜0.05).Conclusion Astragaloside Ⅳ can improve cardiac dysfunction and inhibit myocardial hypertrophy in CHF rats,which may be related to the regulation of PI3 K/Akt/GSK3 β signaling pathway.
王林燕;李超;马明怡;盛晓生
金华市人民医院心血管内一科,浙江金华 321000
中医学
黄芪甲苷;慢性心力衰竭;磷酸肌醇-3-激酶/蛋白激酶B/糖原合成酶激酶-3β信号通路;脑钠肽;游离脂肪酸
Astragaloside Ⅳ;chronic heart failure;phosphoinositide-3-kinase/protein kinase B/glycogen synthase kinase-3β signaling pathway;brain natriuretic peptide;free fatty acid
《中国临床药理学杂志》 2024 (001)
57-61 / 5
金华市重大(重点)科学技术研究计划基金资助项目(2021-3-028)
10.13699/j.cnki.1001-6821.2024.01.012
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