Effect of sildenafil on NLRP3/caspase-1 pathway in the aorta vascular tissue of rat models with erectile dysfunction

Abstract

Objective To investigate the effect of sildenafil (Sil) on the expression of NLRP3/caspase-1 pathway in the aorta vascular tissue of erectile dysfunction (ED) rat models. Methods ED rat model was established and randomly divided into ED group and Sil group. Another 10 rats were selected as control group. After intragastric administration of Sil(20 mg /kg, once a day for 2 weeks), HE staining was used to observe the morphological change of aorta. Aortic fibrosis was detected by Masson staining. The content and distribution of interleukin-1β (IL-1β) and endothelial nitric oxide synthase (eNOS) in aorta were determined by immunohistochemistry. RT-qPCR and Western blot were used to detect the expression of NLRP3, caspase-1, GSDMD, IL-1β and eNOS in the aorta. Results In ED group, there were pathological changes in aortic morphology, more local exfoliation of endothelial cells and obvious fibrosis. The mRNA and protein expressions of NLRP3, caspase-1, GSDMD and IL-1β were increased, and the mRNA and protein expressions of eNOS were decreased in the aorta of the rats in the experimental group(P＜0.05). Compared with the ED group, the aortic morphological changes of the Sil group were improved, the local endothelial cell shedding was reduced, and the fibrosis was alleviated. The mRNA and protein expression of NLRP3, caspase-1, GSDMD and IL-1β decreased, while the mRNA and protein expression of eNOS increased in aorta(P＜0.05). Conclusions The expression of NLRP3/caspase-1 pathway protems in the aorta vescular tissue of rats with ED is up-regulated by Sil, which may improve the inflammatory response, vascular fibrosis and endothelial dysfunction by inhibiting the NLRP3/caspase-1 pathway in the aorta vascular tissue of rats with ED