文献类型：期刊文献

中文题名：当归黄芪胶囊对心力衰竭大鼠心肌自噬的影响

英文题名：Effects of Angelica Sinensis and Astragalus capsules on myocardial autophagy in rats with heart failure

作者：吴雪[1,2,3,4];吕欣芳[1,3,5];支晓东[1,3,5];赵信科[1,3,5];李应东[1,3,5]

第一作者：吴雪

机构：[1]甘肃中医药大学中西医结合学院,甘肃兰州730030;[2]兰州大学第二医院心血管内科,甘肃兰州730030;[3]甘肃省中医药防治慢性疾病重点实验室,甘肃兰州730030;[4]兰州大学第二临床医学院,甘肃兰州730030;[5]甘肃中医药大学附属医院心血管内科,甘肃兰州730030

第一机构：甘肃中医药大学中西医结合学院

年份：2024

卷号：40

期号：10

起止页码：1453

中文期刊名：中国临床药理学杂志

外文期刊名：The Chinese Journal of Clinical Pharmacology

收录：CSTPCD;;北大核心:【北大核心2023】；CSCD:【CSCD2023_2024】；

基金：中医药防治重大疾病科研课题基金资助项目(ZGKZD-2018-2);甘肃省科技重大专项计划基金资助项目(20ZD7FA002);甘肃省科技计划基金资助项目(21JR7RA399);甘肃省教育厅揭榜挂帅基金资助项目(2021jyjbgs-03);兰州市科技局基金资助项目(2023-QN-191,2018-ZD-1);兰州大学第二医院萃英科技创新基金资助项目(CY2021-BJ-A17)。

语种：中文

中文关键词：当归黄芪胶囊;心力衰竭;自噬;磷脂酰肌醇3-激酶;蛋白激酶B;西罗莫司靶蛋白;微管相关轻链蛋白3Ⅱ/Ⅰ

外文关键词：Angelica sinensis and Astragalus capsule;heart failure;autophagy;phosphatidylinositol 3 kinase;protein kinase B;mammalian target of sirolimus;microtubule associated light chain protein 3-Ⅱ/Ⅰ

摘要：目的探讨当归黄芪胶囊是否通过磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/西罗莫司靶蛋白(mTOR)信号通路调控心力衰竭大鼠心肌的自噬。方法用2.5 mg·kg^(-1)阿霉素腹腔注射构建心力衰竭大鼠模型,另取8只为空白组。将造模成功的大鼠随机分为模型组、对照组和低、中、高剂量实验组。对照组给予腹腔注射30 mg·kg^(-1)的3-甲基腺嘌呤;低、中、高剂量实验组分别灌胃给予150、300、450 mg·kg^(-1)的当归黄芪胶囊;空白组及模型组均灌胃给予等量无菌蒸馏水。6组大鼠每天给药1次,持续6周。用超声多普勒检测心功能,用蛋白印迹法检测心肌组织中PI3K、Akt、mTOR、选择性自噬接头蛋白(P62)、微管相关轻链蛋白3Ⅱ/Ⅰ(LC3Ⅱ/Ⅰ)的表达水平。结果空白组、模型组、对照组和高剂量实验组的左心室射血分数分别为(85.00±3.63)%、(56.75±4.83)%、(75.63±3.70)%和(72.75±4.23)%,PI3K相对表达水平分别为1.00±0、0.28±0.05、0.64±0.08和0.74±0.16,磷酸化Akt/Akt分别为1.00±0、0.49±0.06、0.90±0.16和0.95±0.10,磷酸化mTOR/mTOR分别为1.00±0、0.42±0.09、0.73±0.13和0.83±0.08,P62相对表达水平分别为1.00±0、0.24±0.12、0.57±0.09和0.96±0.10,LC3Ⅱ/Ⅰ相对表达水平分别为1.00±0、4.31±0.75、2.20±0.76和1.59±0.24。与模型组比较,高剂量实验组和对照组的上述指标在统计学上差异均有统计学意义(均P<0.05)。结论当归黄芪胶囊能通过调控PI3K/Akt/mTOR通路,抑制心力衰竭大鼠心肌的自噬,从而改善大鼠的心功能。
Objective To investigate whether Angelica Sinensis and Astragalus capsules(AAC)regulates myocardial autophagy in heart failure rats via the phosphatidylinositol 3 kinase(PI3K)/protein kinase(Akt)/mammalian target of sirolimus(mTOR)signaling pathway.Methods A rat model of heart failure was constructed by intraperitoneal 2.5 mg·kg^(-1)doxorubicin,and another 8 rats served as the control group.The modeling rats were randomly divided into model group,control group and experimental-L,-M,-H groups.Control group was given 30 mg·kg^(-1)3-methyladenine by intraperitoneal injection;experimental-L,-M,-H groups were given 150,300 and 450 mg·kg^(-1)AAC by gavage,respectively;blank and model groups were given the same quantity of sterile distilled water.Six groups were administered once daily for 6 weeks.The cardiac function was measured by ultrasound,and the expression levels of PI3K,Akt,mTOR,sequestosome 1(P62)and microtubule-associated light chain protein 3-Ⅱ/Ⅰ(LC3Ⅱ/Ⅰ)in myocardial tissue were measured by Western blot.Results In the blank,model,control and experimental-H groups,the left ventricular ejection fraction values were(85.00±3.63)%,(56.75±4.83)%,(75.63±3.70)%and(72.75±4.23)%;the relative expression levels of PI3K were 1.00±0,0.28±0.05,0.64±0.08 and 0.74±0.16;phosphorylated Akt/Akt were 1.00±0,0.49±0.06,0.90±0.16 and 0.95±0.10;phosphorylated mTOR/mTOR values were 1.00±0,0.42±0.09,0.73±0.13 and 0.83±0.08;the relative expression levels of P62 proteins were 1.00±0,0.24±0.12,0.57±0.09 and 0.96±0.10;the relative expression levels of LC3Ⅱ/Ⅰproteins were 1.00±0,4.31±0.75,2.20±0.76 and 1.59±0.24,respectively.Compared to the model group,statistical significant were identified in the experimental-H and control groups(all P<0.05).Conclusion AAC can regulate PI3K/Akt/mTOR pathway,inhibit myocardial autophagy and improve cardiac function in rats with heart failure.