Chinese Journal of Clinical Anatomy ›› 2022, Vol. 40 ›› Issue (1): 49-54.doi: 10.13418/j.issn.1001-165x.2022.1.10

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Effects of levosimendan on myocardial fibrosis and cardiac function following myocardial infarction in rats

Liu Yali1,  Li Chunyan1, Li Yali2, Kou Huifen1, Xu Xiaowei1, Li Xinjun1*   

  1. 1.Department of Internal Medicine-Cardiovascular; 2.Comprehensive Disease Area,  The Second Affiliated Hospital of Hebei North University, Zhangjiakou 075100, Hebei Province, China
  • Received:2020-06-19 Online:2022-01-25 Published:2022-01-19

Abstract: Objective  To investigate the effect of levosimendan on myocardial infarction (MI) myocardial fibrosis and its mechanism.   Methods   MI model was induced by ligation of left anterior descending coronary artery. Thirty surviving MI rats were randomly divided into a model group and a Levo group (15 rats in each group). Rats in the sham group (n=10) underwent the same surgical procedure, except for no arterial ligation. Levosimendan (4.67 μg·kg-1·d-1) was infused into stomach for 28 days in Levo group. At the same time, rats in sham group and model group were given equal amount of distilled water. 2D echocardiography was adopted to evaluate the cardiac function. Masson-trichrome were used to evaluate the degree of myocardial fibrosis. The expression of COL1A1, COL3A1 mRNA and SIRT1/TGF-β1/Smad3 signaling pathway proteins were detected by quantitative reverse transcription PCR (RT-qPCR) and Western blot, respectively.    Results   Compared with the model group, 2D echocardiography result showed that the LVED of Levo group decreased significantly (P<0.05), while the EF and FS increased significantly (P<0.01). Masson-trichrome result showed that levosimendan treatment significantly reduced necrosis and the content of collagen deposition and inhibited infiltration of inflammatory cells. RT-qPCR analysis result showed that levosimendan treatment significantly reduced the content of type Ⅰ and type Ⅲ collagen in the heart tissue of MI rats (P<0.01). Western blot showed that  levosimendan treatment could significantly up-regulate SIRT1 protein expression  and down-regulate TGF-β1(60%) and p-Smad3 (47%) protein expression (P<0.01).  Conclusions   Levosimendan has anti-fibrotic and cardio-protective effects. These effects are potentially mediated by SIRT1/TGF-β1/Smad3 signaling pathway.

Key words: Levosimendan; ,  , Myocardial infarction; ,  , Rat; ,  , Myocardial fibrosis; ,  , Cardiac function, SIRT

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