Abstract:Objective: To explore the protective effect of neuropilin-1 overexpression on cardiac function and against myocardial tissue injury in rats with isoproterenol (ISO) induced heart failure (HF). Methods: The adenovirus vector of neuropilin-1 overexpression (Ad-neuropilin-1) was constructed. The overexpression efficiency was detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Sixty SD rats were enrolled and randomly divided into control group, ISO group, ISO+Ad group (negative control group) and ISO+Ad-neuropilin-1 group. Except control group, subcutaneous injection of ISO was conducted to prepare HF rats models. The cardiac function in each group was detected. The levels of myocardial damage markers and inflammatory factors in each group were detected by RT-PCR and enzyme-linked immunosorbent assay (ELISA). The apoptosis of myocardial cells was observed by HE staining and TdT-medated dUTP nick end labeling (TUNEL) staining. The expression of proliferation cells related antigen Ki-67 and cysteine aspartase-3 (Cas3) was detected by Western blot. Results: Compared with control group, neuropilin-1 mRNA and protein in ISO+Ad-neuropilin-1 group were increased (P<0.05). Compared with control group, heart rate (HR), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and expression levels of neuropilin-1 and Ki-67 proteins were significantly decreased in ISO group, while levels of serum cardiac troponin (cTnI), creatine kinase (CK), creatine kinase-MB (CK-MB), inducible nitric oxide synthase (iNOS) and interleukin-10 (IL-10) mRNA, apoptosis rate of myocardial cells and level of cleaved caspase-3/Cas3 were significantly increased (P<0.05). Compared with ISO group, HR, LVFS, LVEF, and relative expression of neuropilin-1 and Ki-67 proteins in ISO+Ad-neuropilin-1 group were significantly increased, while cTnI, CK, CK-Mb, iNOS, content of peripheral blood IL-10 mRNA, apoptosis rate of myocardial cells, and level of cleaved caspase-3/Cas3 were significantly decreased (P<0.05). Conclusion: Neuropilin-1 overexpression can inhibit cardiomyocytes apoptosis and inflammation response in rats with ISO-induced HF, and improve their cardiac function.
