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,LC3 Ⅱ/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.
Abstract
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(LC3 Ⅱ/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 LC3 Ⅱ/Ⅰ proteins 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.
基金项目
中医药防治重大疾病科研课题(ZGKZD-2018-2)
甘肃省科技重大专项(20ZD7FA002)
甘肃省科技计划(21JR7RA399)
甘肃省教育厅揭榜挂帅基金(2021jyjbgs-03)
兰州市科技局项目(2023-QN-191)
兰州市科技局项目(2018-ZD-1)
兰州大学第二医院萃英科技创新基金(CY2021-BJ-A17)
国家科技期刊平台
NSTL
万方数据