Xia Ran, Wang Wei, Gao Bing, Ma Qiang, Wang Jing, Dai Xiaohua, Li Qingling
Graduate School, Anhui University of Chinese Medicine, Hefei, Anhui 230012, P.R. China.
Key Laboratory of Xin'an Medicine of Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui 230038, P.R. China.
Exp Ther Med. 2022 May;23(5):359. doi: 10.3892/etm.2022.11286. Epub 2022 Mar 30.
Moxibustion (MOX) is a traditional Chinese medicine preparation, which has been clinically used to treat cardiac diseases in recent years. The present study aimed to examine the protective effects and possible mechanisms of MOX on doxorubicin (DOX)-induced chronic heart failure (CHF) in rats. The animals were divided into five groups, including the Control (normal saline), DOX (doxorubicin 15 mg/kg), MOX (doxorubicin 15 mg/kg + moxibustion), BEN (doxorubicin 15 mg/kg + benazepril 0.86 mg/kg) and MOX + BEN (doxorubicin 15 mg/kg + moxibustion + benazepril 0.86 mg/kg) groups. After three weeks, echocardiography was performed to assess cardiac function and structure, including left ventricular internal diameter in systole, ejection fraction and fractional shortening (FS). Serum brain natriuretic peptide levels and adenosine triphosphate (ATP) levels were measured by enzyme-linked immunosorbent assay and ATP assay. Cardiac pathology was assessed by hematoxylin and eosin and Masson's trichrome staining. Cardiac ultrastructure and the number of autophagosomes formed were visualized by transmission electron microscopy. Western blotting was performed to assess mitochondrial dynamics, autophagy proteins and mitochondrial autophagy-related pathway proteins. The expression levels of these genes were assessed by reverse transcription-quantitative PCR. The results indicated MOX could improve cardiac function, increased cardiac ATP levels and reduced myocardial fibrosis. Western blotting indicated that MOX treatment elevated the expression of optic atrophy 1 protein (OPA1), while decreasing the expression of dynamin-related protein 1 and mitochondrial fission 1 protein. In addition, MOX inhibited autophagy, as evidenced by decreased number of autophagosomes, reduced LC3II/LC3I ratio and increased p62 expression. Furthermore, MOX downregulated DOX-induced FUNDC1 signaling pathway. In summary, MOX has protective effects on DOX-induced CHF in rats, promoting mitochondrial fusion while inhibiting mitochondrial fission and mitophagy. The underlying mechanisms may be related to the inhibition of the FUNDC1 signaling pathway.
艾灸是一种中药制剂，近年来已在临床上用于治疗心脏病。本研究旨在探讨艾灸对阿霉素（DOX）诱导的大鼠慢性心力衰竭（CHF）的保护作用及可能机制。将动物分为五组，包括对照组（生理盐水）、DOX组（阿霉素15mg/kg）、艾灸组（阿霉素15mg/kg+艾灸）、贝那普利组（阿霉素15mg/kg+贝那普利0.86mg/kg）和艾灸+贝那普利组（阿霉素15mg/kg+艾灸+贝那普利0.86mg/kg）。三周后，进行超声心动图检查以评估心脏功能和结构，包括左心室收缩内径、射血分数和缩短分数（FS）。采用酶联免疫吸附测定法和ATP测定法检测血清脑钠肽水平和三磷酸腺苷（ATP）水平。通过苏木精-伊红染色和Masson三色染色评估心脏病理学。通过透射电子显微镜观察心脏超微结构和形成的自噬体数量。进行蛋白质免疫印迹法以评估线粒体动力学、自噬蛋白和线粒体自噬相关途径蛋白。通过逆转录-定量PCR评估这些基因的表达水平。结果表明，艾灸可改善心脏功能，提高心脏ATP水平并减少心肌纤维化。蛋白质免疫印迹法表明，艾灸治疗可提高视神经萎缩蛋白1（OPA1）的表达，同时降低动力相关蛋白1和线粒体分裂蛋白1的表达。此外，艾灸抑制自噬，表现为自噬体数量减少、LC3II/LC3I比值降低和p62表达增加。此外，艾灸下调DOX诱导的FUNDC1信号通路。总之，艾灸对DOX诱导的大鼠CHF具有保护作用，可促进线粒体融合，同时抑制线粒体分裂和线粒体自噬。其潜在机制可能与抑制FUNDC1信号通路有关。
