The effect of ultrasound-guided intraperitoneal injection of ulinastatin on lung development in intrauterine growth-restricted fetal rabbits

Abstract

Objectives

To investigate the effect and mechanism of ulinastatin (UTI) on development of lungs in fetal rabbits with intrauterine growth retardation (IUGR).

Methods

Twenty pregnant rabbits were equally divided into normal, IUGR, UTI, and LY groups. The normal group was only injected with saline and marked with tattoo ink. IUGR models were established by injecting N-nitro-L-arginine methyl ester in the rabbits of IUGR, UTI, and LY groups. The three groups were injected with saline, UTI, or UTI + LY294002 (PI3K inhibitor) respectively, and then marked with tattoo ink. After cesarean section, neonatal weights, and levels of dipalmitoyl phosphatidylcholine (DPPC), nitric oxide (NO), P-Akt, P-eNOS, and pulmonary surfactant-associated protein A (SP-A) were determined in tissues of the lungs. Radial alveoli count (RAC), pulmonary interstitial ratio, and ultrastructural changes in type II alveolar epithelial cells (AEC II) were also determined through light and electron microscopy.

Results

Compared with control, the IUGR group showed significantly decreased weight, RAC, lamellar bodies in AEC II, and levels of P-Akt, P-eNOS, DPPC, NO, and SP-A, and increased pulmonary interstitial ratio (p < .05). The UTI treatment did not affect the weight; however, all other parameters were opposite to those observed in the IUGR group (p < .05). Furthermore, these UTI-mediated changes were inhibited by LY294002.

Conclusions

Intraperitoneal UTI injection can promote the development of lungs and increase pulmonary surfactant production in IUGR fetal rabbits, potentially by activating PI3K/Akt/eNOS/NO signaling.

Keywords:

• Ulinastatin
• nitric oxide
• ultrasound-guided
• intrauterine growth retardation
• lung development

Authors’ contributions

He Shaozheng: Conceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Writing – Original Draft; Lai Weicheng: Conceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Writing – Original Draft; Lyu Guo-Rong: Conceptualization, Validation, Formal analysis, Writing – Review & Editing, Project administration, Funding acquisition; Zheng Xinying: Methodology, Investigation, Visualization.

Ethical approval

The protocols and procedures used for this animal study were approved by the medical ethics audit of the second affiliated hospital of Fujian Medical University.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data used to support the findings of this study will be available from the corresponding author upon reasonable request.

Additional information

Funding

The present study was supported by Quanzhou High Level Talent Support Project Quanzhou Science and Technology Program [2018C071R] and the Fujian Province Health and Family Planning Scientific Research Talent Training Project [2017-CXB-9].