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当归黄芪胶囊对心力衰竭大鼠心肌自噬的影响

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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.
Effects of Angelica Sinensis and Astragalus capsules on myocardial autophagy in rats with heart failure
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.

Angelica sinensis and Astragalus capsuleheart failureautophagyphosphatidylinositol 3 kinaseprotein kinase Bmammalian target of sirolimusmicrotubule associated light chain protein 3-Ⅱ/Ⅰ

吴雪、吕欣芳、支晓东、赵信科、李应东

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甘肃中医药大学中西医结合学院,甘肃兰州 730030

兰州大学第二医院心血管内科,甘肃兰州 730030

甘肃省中医药防治慢性疾病重点实验室,甘肃兰州 730030

兰州大学第二临床医学院,甘肃兰州 730030

甘肃中医药大学附属医院心血管内科,甘肃兰州 730030

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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3 Ⅱ/Ⅰ

中医药防治重大疾病科研课题甘肃省科技重大专项甘肃省科技计划甘肃省教育厅揭榜挂帅基金兰州市科技局项目兰州市科技局项目兰州大学第二医院萃英科技创新基金

ZGKZD-2018-220ZD7FA00221JR7RA3992021jyjbgs-032023-QN-1912018-ZD-1CY2021-BJ-A17

2024

中国临床药理学杂志
中国药学会

中国临床药理学杂志

CSTPCD北大核心
影响因子:1.91
ISSN:1001-6821
年,卷(期):2024.40(10)
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