Jiajun Chen, Huijiao Xu, Li Yang, Feifan Chen, Kunpeng Li, Bing Xu, Wenying Liu, Fang Hou
Sichuan Provincial People’s Hospital and University of Electronic Science and Technology of China School of Medicine.
China
Pediatric Surgery International
Pediatr Surg Int 2025; 42:
DOI: 10.1007/s00383-025-06257-7
Abstract
Purpose: To investigate vasoactive intestinal peptide (VIP) expression and distribution in fetal Sprague-Dawley (SD) rat lung with congenital diaphragmatic hernia (CDH). Assess the impact of VIP analog Aviptadil on CDH-associated lung hypoplasia
Methods: CDH was induced in pregnant SD rats by nitrofen gavage on E9.5. The CDH + VIP group received Aviptadil via tail vein from E10.5. Lung development was assessed by hematoxylin and eosin (HE) staining. VIP, α-SMA, and CD31 were evaluated by immunofluorescence (IF). VIP mRNA and protein levels were quantified by RT-qPCR and Western blotting.
Results: The CDH group exhibited a significantly lower lung index compared to the control group (P < 0.001), with no significant difference observed between the CDH and CDH + VIP groups. Compared to controls, VIP expression in CDH lungs was significantly downregulated at both the mRNA (P = 0.049) and protein levels (P = 0.049). HE staining revealed mature alveolar structures in the control group, whereas the CDH group showed disrupted pulmonary architecture. Partial improvement was observed in the CDH + VIP group. IF analysis indicated that VIP was predominantly localized in the bronchi. VIP fluorescence intensity was significantly decreased in the CDH group compared to both the control group (P = 0.002) and the CDH + VIP group (P = 0.005), while no significant difference was found between the CDH + VIP and control groups. α-SMA fluorescence was primarily localized to pulmonary arterioles and bronchial smooth muscle. Compared to the control group, α-SMA expression was significantly upregulated in the CDH group (P < 0.001). The CDH + VIP group showed a significant reduction in α-SMA expression compared to the CDH group (P = 0.026), with no significant difference from the control group. CD31 was mainly localized to the vascular endothelium. CD31 fluorescence intensity was markedly increased in the CDH group compared to both the control (P < 0.001) and CDH + VIP groups (P < 0.001). The CDH + VIP group also had significantly higher CD31 levels than the control group (P = 0.005).
Conclusion: This study revealed that VIP is downregulated in CDH lungs. In this nitrofen-induced SD rat model, Aviptadil partially restored VIP levels and was associated with attenuation of vascular remodeling and alveolar dysplasia, suggesting a possible therapeutic role in CDH-related pulmonary hypoplasia that warrants further investigation.
Category
Class III. Pulmonary Hypertension Associated with Lung Hypoplasia
Animal Models of Pulmonary Vascular Disease and Therapy
Pulmonary Vascular Pathology
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
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