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Purpose <p>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.</p> Methods <p>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.</p> Results <p>The CDH group exhibited a significantly lower lung index compared to the control group (<i>P</i> &lt; 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 (<i>P</i> = 0.049) and protein levels (<i>P</i> = 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 (<i>P</i> = 0.002) and the CDH + VIP group (<i>P</i> = 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 (<i>P</i> &lt; 0.001). The CDH + VIP group showed a significant reduction in α-SMA expression compared to the CDH group (<i>P</i> = 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 (<i>P</i> &lt; 0.001) and CDH + VIP groups (<i>P</i> &lt; 0.001). The CDH + VIP group also had significantly higher CD31 levels than the control group (<i>P</i> = 0.005).</p> Conclusion <p>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.</p>

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Investigation of vasoactive intestinal peptide expression and significance in a congenital diaphragmatic hernia animal model

  • 期刊论文

  • 发表日期：

    2025年12月4日

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  • Jiajun Chen,
  • Huijiao Xu,
  • Li Yang,
  • Feifan Chen,
  • Kunpeng Li,
  • Bing Xu,
  • Wenying Liu,
  • Fang Hou

摘要

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.