〔Abstract〕 Objective 　To investigate the effects of C1q tumor necrosis factor-related protein 3 (CTRP3)-enhanced Sendai virus (SeV) vector-overexpressing Gata4, Mef2c, and Tbx5 (SeVGMT) in the treatment of myocardial infarction (MI) mice and to analyze whether ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) mediates this therapeutic pathway. Methods 　The mice were divided into 7 groups ( n=12): Sham group, MI group, SeVGMT group, CTRP3-Lv group, UCHL1-sh group, SeVGMT+CTRP3-Lv group, and SeVGMT+CTRP3-Lv+UCHL1-sh group. In the Sham group, only the skin was incised without ligation, while the coronary artery was ligated 2-3 mm below the left atrial appendage in mice in other groups. PBS was injected at three points in the myocardial infarction boundary in the Sham and MI groups 30 minutes after ligation. Mice in other groups were injected with SeVGMT, CTRP3-Lv, or UCHL1-sh according to their grouping. Four weeks after treatment, fractional shortening (FS), ejection fraction (EF), left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), heart rate (HR), mean arterial pressure (MAP), serum creatine kinase isoenzyme MB (CK-MB), myocardial troponin I (cTnI) and lactate dehydrogenase (LDH) levels, and myocardial tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels in mice were detected. The pathological changes of myocardial tissue were detected by 2,3,5-triphenyltetrazolium chloride (TTC), hematoxylin-eosin (HE), Masson trichrome and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The mRNA expressions of CTRP3 and UCHL1 were detected by qRT-PCR. The protein expressions of CTRP3, UCHL1, collagen Ⅰ, collagen Ⅲ, Bcl-2-associated X (Bax) and B-cell lymphoma/leukemia-2 (Bcl-2) in myocardial tissue were detected by Western blot or immunohistochemical staining. Results 　Compared with SeVGMT group and CTRP3-Lv group, the levels of EF, FS, HR and MAP in SeVGMT+CTRP3-Lv group increased ( P<0.05). The levels of LVIDd, LVIDs, CK-MB, cTnI, LDH, TNF-α, IL-1β and IL-6 decreased ( P<0.05). MI area, fibrosis area and TUNEL positive rate decreased ( P<0.05), the protein levels collagen Ⅰ, collagen Ⅲ and Bax decreased ( P<0.05), and Bcl-2 protein levels increased ( P<0.05). The mRNA and protein levels and relative staining intensity of CTRP3 and UCHL1 increased ( P<0.05). Compared with SeVGMT+CTRP3-Lv group, the addition of UCHL1-sh treatment (SeVGMT+CTRP3-Lv+UCHL1-sh group) significantly weakened the influence of SeVGMT+CTRP3-Lv on the above indexes ( P<0.05). Conclusion 　 CTRP3 mediated UCHL1 enhances the therapeutic effect of SeVGMT reprogrammed CFs on MI in mice.