Phosphodiesterase-5 Inhibitor Sildenafil Pretreatment Attenuates Apoptosis and Intestinal Injury in a Rat Model of Necrotizing Enterocolitis
Abstract
Abstract Background Necrotising enterocolitis (NEC) is a devastating gastrointestinal disease of premature infants, in which hypoxia-induced apoptosis plays a critical role in intestinal epithelial injury. The balance between pro-apoptotic and anti-apoptotic proteins, particularly Bax and Bcl-2, as well as the hypoxia-responsive transcription factor HIF-1α, are key determinants of epithelial survival.. Sildenafil citrate, a phosphodiesterase-5 inhibitor, has been shown to improve microcirculation and exert anti-apoptotic effects through nitric oxide–cGMP signalling, but its role in NEC remains poorly understood.This study aimed to evaluate the protective effects of sildenafil on NEC-induced apoptosis in rat pups. Methods A total of 75 Wistar rat pups were randomly assigned to six groups: control, NEC, SF + DMSO, and sildenafil-treated groups (1, 5, and 10 mg/kg/day). Sildenafil was administered intraperitoneally for 4 days before NEC induction. NEC was induced by hypoxia (100% nitrogen for 60 seconds, twice daily for 48 hours) and followed by cold stress (10 minutes at 4°C).Intestinal tissues were collected for histopathological scoring, caspase-3 immunohistochemistry, and quantitative RT-PCR analysis of HIF-1α, Bax, and Bcl-2 expression. Data were analyzed using ANOVA and Kruskal–Wallis tests, with p ≤ 0.05 considered statistically significant Results NEC pups exhibited severe villous damage, elevated histological injury scores, and marked upregulation of HIF-1α and Bax,…
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