Effect of epidermal growth factor and dexamethasone on fetal rat lung development

ArticleinChinese medical journal 122(17):2013-6 · September 2009with8 Reads
DOI: 10.3760/cma.j.issn.0366-6999.2009.17.010 · Source: PubMed
Epidermal growth factor (EGF), a mitogenic polypeptide that binds to cell surface receptors, is an important regulator of cell differentiation and fetal lung surfactant synthesis. We investigated the preventive and therapeutic effects of EGF in respiratory distress syndrome, by administering EGF and dexamethasone (Dex) to mother rat before delivery. Six female Sprague-Dawley (SD) rats were assigned to three groups (2 rats each); EGF or Dex was given to pregnant rats (EGF group and Dex group, respectively) from gestational day 16 to day 18 by intraperitoneal injection, while the group with normal saline injection was used as negative controls. Fetal rats were taken out of womb by hysterotomy on day 19 of pregnancy, then 24 fetal rats were randomly chosen from each group. Their body weights were measured, and pulmonary surfactant protein-A and -B (SP-A and SP-B) antigens were determined by immunohistochemical staining in each group. The histologic structure was examined under a light microscope, a light microscopic image system or an electron microscope. The expressions of SP-A and SP-B could be detected in each group. A significant difference was observed for SP-A and SP-B in the EGF and Dex groups compared with the control group (P < 0.01). Image analysis showed that the relative values of air space area and interalveolar septa area in the EGF and Dex groups were significantly greater than those in the control group (P < 0.01), while no significant difference was found between the two groups (P > 0.05). The ultrastructural features of fetal lungs showed that the number of alveolar type II cells containing lamellar bodies in the EGF and Dex groups was apparently increased compared with that in the control group. The mean body weight of fetus from the Dex group was smaller than that from the control group ((1.3192 +/- 0.0533) g, (1.3863 +/- 0.0373) g), but there was no significant difference between the EGF group and the control group ((1.3986 +/- 0.0730) g, (1.3863 +/- 0.0373) g). Maternal treatment with EGF and Dex on days 16 - 18 of gestation could promote morphogenesis and increase the surfactant levels in premature fetal lung. However, maternal treatment with Dex, not EGF, decreased the body weight.
  • [Show abstract] [Hide abstract] ABSTRACT: Liver fibrosis is the process through which numerous chronic liver diseases develop into liver cirrhosis. Leptin can activate hepatic stellate cells (HSCs) and play an important role in the formation of liver fibrosis. However, the process by which leptin activates HSCs is complicated, and research on this process is limited. The aim of this study was to explore the related changes in gene expression and the control mechanisms involved in leptin activated HSCs to understand the overall mechanism of liver fibrosis development. We cultivate rat HSCs, with and without stimulation by leptin, and extracted mRNA. Differentially expressed genes were detected by microarray analysis. The differentially expressed genes identified included six upregulated genes and six downregulated genes. The representative upregulated genes included short chain dehydrogenase (CY5/CY3 = 2.265) and pulmonary surfactant protein A1 (CY5/CY3 = 2.036). The significant downregulated gene encoded hepatic stearoyl coenzyme A desaturase 1 (SCD-1) (CY5/CY3 = 0.351). Leptin might mediate the molecular biological mechanisms of liver fibrosis.
    Article · Mar 2010
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Pulmonary surfactant (PS) administration has been attempted for the treatment of adults with acute lung injury (ALI)/adult respiratory distress syndrome. Aerosolized surfactants inhaled by spontaneous breathing may be an effective method of surfactant-based therapies. Using a noninvasive apparatus, we evaluated the therapeutic effects of aerosolized PS alone or together with dexamethasone (Dex) on a rat model of ALI. Methods: Severe ALI was induced by intravenous injection of 20% oleic acid (0.2 mL/kg) into adult Sprague-Dawley rats. Animals were divided into eight groups: sham (n = 10); model (injury only, n = 10); normal saline (NS) aerosol driven by compressed air (air-NS, n = 13); PS aerosol driven by compressed air (air-PS, n = 13); NS aerosol driven by O2 (O2-NS, n = 13); PS aerosol driven by O2 (O2-PS, n = 13); Dex aerosol driven by O2 (O2-Dex, n = 13); and PS and Dex aerosol driven by O2 (O2-PS-Dex, n = 13). Blood gases, breathing rate, lung index, total protein, and proinflammatory cytokines (tumor necrosis factor-α, interleukin 1β, interleukin 6) in the bronchoalveolar lavage fluid (BALF), and lung histology were examined. Results: Animals treated with air-PS for 20 minutes had significantly improved lung function, reduced pulmonary edema, decreased concentration of total protein and proinflammatory cytokines in BALF, ameliorated lung injury, and improved animal survival. In the O2-PS group, the breathing rates and lung injury scores were significantly lower than that of the air-PS group. In the O2-PS-Dex group, lung edema, total protein, and inflammatory cytokines in BALF were significantly reduced in comparison with the O2-PS group. Conclusion: Inhalation of aerosolized PS generated by the noninvasive apparatus could significantly reduce lung injury, while using oxygen line available in the clinical wards to generate PS aerosol is more convenient and adds further benefits. This method can also be used to deliver Dex and other therapeutic agents to ameliorate lung injury.
    Article · Sep 2012