The Downregulation Of Cd47 Attenuates Apoptosis And Inflammation By Inhibiting Inos Activity In A Rat Model Of Myocardial Ischemia/Reperfusion Injury

Objective: Apoptosis and inflammation play critical roles in myocardial ischemia/reperfusion (I/R) injuries (MIRI). Various studies have demonstrated that CD47 can aggravate apoptosis and inflammation in various pathological processes. The purpose of the present study was to verify whether the downregulation of CD47 exerts a protective effect against myocardial apoptosis and inflammation during MIRI. Methods: Adult SD rats (n=60) were divided into 4 groups as follows: The sham group, the I/R group, the Ad-Control group, and the Ad-siCD47 group. A myocardial I/R model was established three days after the gene delivery. CK, The LDH levels were measured and the myocardial histomorphology was assessed to evaluate the myocardial damage. The infarct area was assessed using Evans Blue/TTC staining. A TUNEL assay was performed to measure the apoptosis. ELISA kits were used to measure the inflammatory mediator levels, such as IL-1 beta, IL-6, and TNF-alpha. The NO expressions and the iNOS activity were also measured. The iNOS, Bax, and caspase-3 protein expression levels were evaluated using western blot. The related mRNA levels were evaluated using RT-qPCR. Results: The results revealed that Ad-siCD47 significantly decreased the CD47 expression. In addition, with the downregulation of CD47, the infarct size, the CK and LDH levels, and the Bax, caspase-3, IL-1 beta, IL-6, and TNF-alpha expressions, as well as the iNOS activity and the NO content were significantly reduced. Conclusions: The downregulation of CD47 reduces apoptosis and inflammation by inhibiting the expression and activity of iNOS, so it may be a therapeutic target for MIRI.