Effects of gene knockdown of CNP on ventricular remodeling after myocardial ischemia‐reperfusion injury through NPRB/Cgmp signaling pathway in rats

This study aimed to explore effects of CNP on ventricular remodeling following myocardial ischemia‐reperfusion (I/R) injury through the NPRB/cGMP signaling pathway. Rat cardiomyocytes were assigned into: control, I/R, I/R + CNP, and I/R + 8‐Br‐cGMP groups. ELISA, qRT‐PCR, and Western blotting were used to detect cGMP content and expression, respectively. After model establishment of I/R rats, normal control, CNP−/− control, I/R, and CNP−/− groups were set. Indexes of heart were detected using echocardiography and hemodynamics. ELISA was used to measure serum CNP, cGMP, LDH, cTn I, CK‐MB, TNF‐α, and IL‐6 levels. Myocardial infarct was identified by TTC staining, and apoptosis conditions by TUNEL staining. QRT‐PCR and Western blotting were adopted to detect expressions of CNP, NPRB, cGMP, and apoptosis‐related genes. Compared with control group, cGMP contents and expression in the I/R, I/R + CNP and I/R + 8‐Br‐cGMP groups were decreased. Levels of LVEDV, LVESV, LVDS, LVDD, IVSD, LVM, LVEDP, and LVSP were higher in the I/R, CNP−/− control, and CNP−/−groups than normal control group while LVEF, SV, CO, and ±dp/dtmax were lower. Compared with the normal control group, LDH, cTn I, CK‐MB, TNF‐α, and IL‐6 were higher in the I/R, CNP−/− control and CNP−/− groups; pathological changes and myocardial infarction were observed in the I/R, CNP−/− control, and CNP−/− groups; expressions of apoptosis‐related genes in those groups were higher; while CNP, NPRB, cGMP, and Bcl‐2 expressions were decreased. We came to the conclusion that gene knockdown of CNP blocks the NPRB/cGMP signaling pathway, thereby aggravating myocardial I/R injury and causing ventricular remodeling in rats. In conclusion, the results in this study have demonstrated that gene knockdown of CNP blocks the NPRB/cGMP signaling pathway, which aggravates myocardial I/R injury and causes ventricular remodeling in rats. This study is helpful to investigate the roles of CNP and it would provide some important suggestions for the treatment and diagnosis of ischemic heart diseases in the future. However, this study did not include a large amount of samples, which would impact the results of the experiment to some extent. Therefore, more studies are needed to validate the conclusion in the present study in the following experimental researches.