Abstract
BackgroundLiver dysfunction and cirrhosis affect vasculature in several organ systems and cause impairment of organ functions, thereby increasing morbidity and mortality. Establishment of a mouse model of hepatopulmonary syndrome (HPS) would provide greater insights into the genetic basis of the disease. Our objectives were to establish a mouse model of lung injury after common bile duct ligation (CBDL) and to investigate pulmonary pathogenesis for application in future therapeutic approaches.MethodsEight-week-old Balb/c mice were subjected to CBDL. Immunohistochemical analyses and real-time quantitative reverse transcriptional polymerase chain reaction were performed on pulmonary tissues. The presence of HPS markers was detected by western blot and microarray analyses.ResultsWe observed extensive proliferation of CD31-positive pulmonary vascular endothelial cells at 2 weeks after CBDL and identified 10 upregulated and 9 down-regulated proteins that were associated with angiogenesis. TNF-α and MMP-9 were highly expressed at 3 weeks after CBDL and were less expressed in the lungs of the control group.ConclusionsWe constructed a mouse lung injury model by using CBDL. Contrary to our expectation, lung pathology in our mouse model exhibited differences from that of rat models, and the mechanisms responsible for these differences are unknown. This phenomenon may be explained by contrasting processes related to TNF induction of angiogenic signaling pathways in the inflammatory phase. Thus, we suggest that our mouse model can be applied to pulmonary pathological analyses in the inflammatory phase, i.e., to systemic inflammatory response syndrome, acute lung injury, and multiple organ dysfunction syndrome.
Highlights
Liver dysfunction and cirrhosis affect vasculature in several organ systems, resulting in impairment of organ function that leads to increased morbidity and mortality.[1,2] Hepatopulmonary syndrome (HPS) is a pulmonary vascular disorder associated with liver cirrhosis and is seen in 5–32% of cirrhotic patients in the setting of pulmonary microvascular dilatation-induced defects in arterial oxygenation.[1,2] hepatopulmonary syndrome (HPS) occurs more frequently in patients with severe liver disease, patients with severe hepatic dysfunction do not always have HPS
Fallon et al reported that angiogenesis plays a role in the pathophysiology of HPS and explained the mechanisms underlying the activation of vascular endothelial growth factor A (VEGF-A), which is produced by inflammatory cells such as intravascular monocytes and induces angiogenesis.[10]
Histologic changes in hematoxylin-eosin staining and pulmonary vascular proliferation in immunohistochemical analysis of the lungs are shown in Figures 1B and 2A. These changes were consistent with findings of a murine common bile duct ligation (CBDL) model in which pulmonary angiogenic processes were confirmed by immunostaining imagery.[12]
Summary
Liver dysfunction and cirrhosis affect vasculature in several organ systems, resulting in impairment of organ function that leads to increased morbidity and mortality.[1,2] Hepatopulmonary syndrome (HPS) is a pulmonary vascular disorder associated with liver cirrhosis and is seen in 5–32% of cirrhotic patients in the setting of pulmonary microvascular dilatation-induced defects in arterial oxygenation.[1,2] HPS occurs more frequently in patients with severe liver disease, patients with severe hepatic dysfunction do not always have HPS. Our objectives were to establish a mouse model of lung injury after common bile duct ligation (CBDL) and to investigate pulmonary pathogenesis for application in future therapeutic approaches
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
