Abstract：Objective: To explore the mechanism of the involvement of Transmembrane BAX Inhibitor Motif 1(TMBIM1) in atrial fibrillation (AF). Methods: Forty adult male Sprague-Dawley rats were randomly divided into five groups: control group, AF group, AF+Vector group, AF+TMBIM1 group and AF+TMBIM1+MMP9 agonist (GC) group, with 8 rats in each group. Except the control group, rats in the other groups were injected with acetylcholine (ACh) and calcium chloride (CaCl2) via the tail vein to an induceatrial fibrillation (AF) model. On the 21st day, the left atrial diameter was analyzed by echocardiography, and the induction rate and duration of atrial fibrillation were evaluated via in vivo electrophysiology. The expressions of α -smooth muscle actin (α-SMA) and matrix metalloproteinase 9(MMP9) in atrial tissue were analyzed by Western blot. Rat cardiomyocytes (H9C2) were divided into sh-NC group, sh-TMBIM1 group, carrier group and TMBIM1 group. Among them, the sh-TMBIM1 group and TMBIM1 group established H9C2 with stable TMBIM1 knockdown or upregulation using short hairpin RNA (shRNA) interference or adenovirus AAV9-ANF-TMBIM1 infection. The fluorescence intensities of MMP9, α-SMA and TMBIM1 in H9C2 cells were analyzed by immunofluorescence. Results: Compared with the control group, AF susceptibility, AF duration and atrial fibrosis area of rats in AF group and AF+Vector group were significantly increased (P<0.05). Compared with AF+Vector group, AF susceptibility, AF duration and atrial fibrosis area of rats in AF+TMBIM1 group were significantly decreased (P<0.05). The left atrial diameter and the expression of MMP9 and α-SMA in atrial tissue of rats in AF group and AF+Vector group were significantly higher than those in control group (P<0.05). Compared with the AF+Vector group, the left atrial diameter and the expression of MMP9 and α-SMA in the atrial tissue of rats in the AF+TMBIM1 group were significantly decreased (P<0.05). Compared with AF+TMBIM1 group, AF susceptibility, AF duration, left atrial diameter, atrial fibrosis area and α-SMA expression in atrial tissues of rats in AF+TMBIM1+GC group were significantly increased (P<0.05). Compared with sh-NC group, the fluorescence intensity of TMBIM1 in H9C2 cells in sh-TMBIM1 group was significantly decreased (P<0.05), while the fluorescence intensities of MMP9 and α-SMA were significantly increased (P<0.05). Compared with Vector group, the fluorescence intensity of TMBIM1 in H9C2 cells in TMBIM1 group was significantly increased (P<0.05), while the fluorescence intensities of MMP9 and α-SMA were significantly decreased (P<0.05). Conclusion: In the rat model of AF induced by Ach-CaCl2, TMBIM1 down-regulation can promote atrial remodeling and AF progression through atrial fibrosis mediated by MMP9 signaling pathway.
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2026, Vol. 32 
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