{"title":"Shenge powder inhibits myocardial fibrosis in rats with post-myocardial infarction heart failure through LOXL2/TGF-β1/IL-11 signaling pathway.","authors":"Hang Xie, Boyong Qiu, Haitao Li, Ruoyu Shi","doi":"10.3724/zdxbyxb-2024-0606","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effect of Shenge powder (SGP) on myocardial fibrosis in rats with heart failure after myocardial infarction and its relation with lysyl oxidase like protein 2 (LOXL2)/transforming growth factor-β1 (TGF-β1)/IL-11 signaling pathway.</p><p><strong>Methods: </strong>Seventy-two SPF male SD rats were divided into blank control group, model control group, SGP small dose group, SGP large dose group, positive control group, SGP large dose+LOXL2 activator group, with 12 rats in each group. Except for blank control group, post-myocardial infarction heart failure was induced by coronary constriction in all groups. Corresponding treatments were given immediately after successful modeling, once a day for 4 weeks. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) in rats were detected by Color Doppler ultrasound imaging. Levels of IL-1β and IL-6 in serum were analyzed by ELISA method, Myocardial collagen volume fraction (CVF) was evaluated by Masson staining. Expressions of collagen Ⅰ and α-smooth muscle actin (α-SMA) in myocardial tissue were detected by immunohistochemical staining. The mRNA expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in myocardial tissue were detected by qRT-PCR. Expression of LOXL2, TGF-β1, and IL-11 proteins in myocardial tissue were detected by Western blotting.</p><p><strong>Results: </strong>Compared with the blank control group, the LVFS and LVEF of the model control group decreased, the levels of serum IL-6 and IL-1β elevated, the CVF value, the expressions of collagen Ⅰ and α-SMA in myocardial tissue, expressions of <i>MMP</i>-<i>9</i> and <i>TIMP</i>-<i>1</i> mRNA, and expressions of LOXL2, TGF-β1, and IL-11 proteins increased (all <i>P</i><0.05). Compared with the model control group, the LVFS and LVEF of SGP small dose group, SGP large dose group and positive control group increased, the levels of serum IL-6 and IL-1β decreased, the CVF value, the expressions of Collagen Ⅰ and α-SMA in myocardial tissue, expressions of <i>MMP</i>-<i>9</i> and <i>TIMP</i>-<i>1</i> mRNA, and expressions of LOXL2, TGF-β1, and IL-11 proteins decreased (<i>P</i><0.05); while LOXL2 activator reversed the improvement effect of high-dose SGP on myocardial fibrosis in heart failure rats after myocardial infarction.</p><p><strong>Conclusions: </strong>Shenge powder may inhibit myocardial fibrosis in heart failure rats after myocardial infarction by inhibiting the LOXL2/TGF-β1/IL-11 pathway.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"1-10"},"PeriodicalIF":0.0000,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3724/zdxbyxb-2024-0606","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: To investigate the effect of Shenge powder (SGP) on myocardial fibrosis in rats with heart failure after myocardial infarction and its relation with lysyl oxidase like protein 2 (LOXL2)/transforming growth factor-β1 (TGF-β1)/IL-11 signaling pathway.
Methods: Seventy-two SPF male SD rats were divided into blank control group, model control group, SGP small dose group, SGP large dose group, positive control group, SGP large dose+LOXL2 activator group, with 12 rats in each group. Except for blank control group, post-myocardial infarction heart failure was induced by coronary constriction in all groups. Corresponding treatments were given immediately after successful modeling, once a day for 4 weeks. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) in rats were detected by Color Doppler ultrasound imaging. Levels of IL-1β and IL-6 in serum were analyzed by ELISA method, Myocardial collagen volume fraction (CVF) was evaluated by Masson staining. Expressions of collagen Ⅰ and α-smooth muscle actin (α-SMA) in myocardial tissue were detected by immunohistochemical staining. The mRNA expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in myocardial tissue were detected by qRT-PCR. Expression of LOXL2, TGF-β1, and IL-11 proteins in myocardial tissue were detected by Western blotting.
Results: Compared with the blank control group, the LVFS and LVEF of the model control group decreased, the levels of serum IL-6 and IL-1β elevated, the CVF value, the expressions of collagen Ⅰ and α-SMA in myocardial tissue, expressions of MMP-9 and TIMP-1 mRNA, and expressions of LOXL2, TGF-β1, and IL-11 proteins increased (all P<0.05). Compared with the model control group, the LVFS and LVEF of SGP small dose group, SGP large dose group and positive control group increased, the levels of serum IL-6 and IL-1β decreased, the CVF value, the expressions of Collagen Ⅰ and α-SMA in myocardial tissue, expressions of MMP-9 and TIMP-1 mRNA, and expressions of LOXL2, TGF-β1, and IL-11 proteins decreased (P<0.05); while LOXL2 activator reversed the improvement effect of high-dose SGP on myocardial fibrosis in heart failure rats after myocardial infarction.
Conclusions: Shenge powder may inhibit myocardial fibrosis in heart failure rats after myocardial infarction by inhibiting the LOXL2/TGF-β1/IL-11 pathway.
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