芪红补肺汤通过AMPK/mTOR通路调控低氧性肺动脉高压大鼠的自噬水平研究  

Qihong Bufei Decoction regulates autophagy levels via the AMPK/mTOR pathway in rats with hypoxic pulmonary arterial hypertension

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作  者:兰岚[1] 陈阿贞 陈志斌[1] LAN Lan;CHEN A-zhen;CHEN Zhi-bin

机构地区:[1]福建中医药大学附属第二人民医院,福建福州350003

出  处:《中国疗养医学》2025年第4期14-18,共5页Chinese Journal of Convalescent Medicine

基  金:福建中医药大学校管课题临床专项(XB2023034);福建省名老中医药专家传承工作室建设项目(闽卫中医函[2023]697号)。

摘  要:目的 观察芪红补肺汤对低氧性肺动脉高压(HPAH)大鼠肺动脉压的影响,探讨芪红补肺汤治疗HPAH的可能机制。方法 40只雄性SD大鼠随机分为常氧对照组(N组)、HPAH模型组(H组)、芪红补肺汤治疗组(T组)、芪红补肺汤+Compound C组(T+C组),每组各10只。H组、T组、T+C组给予低压低氧环境建立大鼠HPAH模型。同时各组大鼠给予相关药物干预。干预完成后测定各组大鼠的平均肺动脉压(MPAP)、右心室收缩压(RVSP)及右心室肥厚指数(RVHI);利用透射电镜观察肺组织自噬超微结构;Western blot法检测肺组织腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)和哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)的磷酸化水平及自噬相关蛋白P62、Beclin-1、LC3B的表达。结果 血流动力学指标方面,H组大鼠与N组相比MPAP、RVSP、RVHI均明显升高(P<0.05),T组较H组MPAP、RVSP、RVHI均明显下降(P<0.05),T+C组较T组MPAP、RVSP、RVHI均明显升高(P<0.05)。透射电镜下可见H组大鼠肺组织自噬活跃,T组细胞自噬进一步增加,T+C组自噬活动较T组受到明显抑制。Western blot检测结果,与N组相比,H组p-AMPK、Beclin-l、LC3B表达显著升高,p-mTOR、P62表达显著下降(P<0.05);与H组相比,T组p-AMPK、Beclin-l、LC3B表达进一步升高,p-mTOR、P62表达进一步下降(P<0.05);与T组相比,T+C组p-AMPK、Beclin-l、LC3B表达则显著下降,p-mTOR、P62表达则显著升高(P<0.05)。结论 芪红补肺汤可降低肺动脉压、改善右心室肥厚,其机制可能与其激活AMPK/mTOR信号促进细胞自噬相关。Objective To observe the effects of Qihong Bufei Decoction on the pulmonary arterial pressure in rats with hypoxic pulmonary arterial hypertension(HPAH),and to explore its mechanism.Methods Totally forty male Sprague-Dawley(SD)rats were randomly divided into four groups:normoxia group(N),HPAH group(H),Qihong Bufei Decoction group(T)and Qihong Bufei Decoction+Compound C group(T+C),with 10 rats in each group.Rats in the H group,T group and T+C group received hypobaric hypoxia to establish the HPAH model,followed by drug intervention correspondingly.The mean pulmonary artery pressure(MPAP),right ventricular systolic pressure(RVSP),and right ventricular hypertrophy index(RVHI)were measured after the intervention.The internal ultrastructure of lung tissue was observed by transmission electron microscopy(TEM).The protein levels of AMP-activated protein kinase(AMPK),mammalian target of rapamycin(mTOR),P62,Beclin1l,and light chain 3B(LC3B)in the lung tissue were detected by Western blot.Results Compared with the N group,MPAP,RVSP and RVHI significantly increased in H group(all P<0.05).Compared with the H group,MPAP,RVSP and RVHI were significantly lower in the T group(all P<0.05).Compared with the T group,MPAP,RVSP and RVHI were significantly higher in the T+C group(all P<0.05).Compared with the N group,activated autophagy was observed in the H group,which was more pronounced in the T group but significantly inhibited in the T+C group.The protein expressions of p-AMPK,Beclin-1 and LC3B were significantly up-regulated in the H group than the N group(all P<0.05),while the levels of p-mTOR and P62 protein expression were down-regulated(all P<0.05).Compared with the H group,protein levels of p-AMPK,Beclin-1 and LC3B were further upregulated,and p-mTOR and P62 were downregulated in the T group(all P<0.05).Protein levels of p-AMPK,Beclin-1 and LC3B were significantly downregulated,and p-mTOR and P62 were upregulated in the T+C group than the T group(all P<0.05).Conclusion Qihong Bufei Decoction can reduce pulmonary artery pres

关 键 词:低氧性肺动脉高压 自噬 腺苷酸活化蛋白激酶 哺乳动物雷帕霉素靶蛋白 芪红补肺汤 

分 类 号:R285.5[医药卫生—中药学]

 

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