Shenge powder inhibits myocardial fibrosis in rats with post-myocardial infarction heart failure through LOXL2/TGF-β1/IL-11 signaling pathway

Objective 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. Conclusion Shenge powder may inhibit myocardial fibrosis in heart failure rats after myocardial infarction by inhibiting the LOXL2/TGF-β1/IL-11 pathway.