ABSTRACT
Infection of schistosomiasis japonica may eventually lead to liver fibrosis, and no effective antifibrotic therapies are available but liver transplantation. Hedgehog (HH) signaling pathway has been involved in the process and is a promising target for treating liver fibrosis. This study aimed to explore the effects of pentoxifylline (PTX) on liver fibrosis induced by schistosoma japonicum infection by inhibiting the HH signaling pathway. Phorbol12-myristate13-acetate (PMA) was used to induce human acute mononuclear leukemia cells THP-1 to differentiate into macrophages. The THP-1-derived macrophages were stimulated by soluble egg antigen (SEA), and the culture supernatants were collected for detection of activation of macrophages. Cell Counting Kit-8 (CCK-8) was used to detect the cytotoxicity of the culture supernatant and PTX on the LX-2 cells. The LX-2 cells were administered with activated culture supernatant from macrophages and(or) PTX to detect the transforming growth factor-β gene expression. The mRNA expression of shh and gli-1, key parts in HH signaling pathway, was detected. The mRNA expression of shh and gli-1 was increased in LX-2 cells treated with activated macrophages-derived culture supernatant, suggesting HH signaling pathway may play a key role in the activation process of hepatic stellate cells (HSCs). The expression of these genes decreased in LX-2 cells co-cultured with both activated macrophages-derived culture supernatant and PTX, indicating PTX could suppress the activation process of HSCs. In conclusion, these data provide evidence that PTX prevents liver fibrogenesis in vitro by the suppression of HH signaling pathway.
Subject(s)
Animals , Humans , Antigens, Helminth , Pharmacology , Cell Culture Techniques , Cell Differentiation , Cell Line , Culture Media, Conditioned , Chemistry , Pharmacology , Gene Expression Regulation , Hedgehog Proteins , Genetics , Allergy and Immunology , Hepatic Stellate Cells , Cell Biology , Metabolism , Liver Cirrhosis , Metabolism , Parasitology , Macrophage Activation , Macrophages , Cell Biology , Allergy and Immunology , Models, Biological , Monocytes , Cell Biology , Metabolism , Pentoxifylline , Pharmacology , Phosphodiesterase Inhibitors , Pharmacology , RNA, Messenger , Genetics , Allergy and Immunology , Schistosoma japonicum , Chemistry , Signal Transduction , Tetradecanoylphorbol Acetate , Pharmacology , Zinc Finger Protein GLI1 , Genetics , Allergy and Immunology , Zygote , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To evaluate the results of Fontan operation with extracardiac conduit on beating hearts.</p><p><b>METHODS</b>Forty-two patients (31 males and 11 females) age ranged from 3 to 19 years old included in this study. There were 19 double inlet-ventricle, 10 tricuspid atresia, and 3 patients with mitral atresia, 10 patients with other complex congenital cardiac malformations. Fontan operations with extracardiac conduit were performed in all patients with the help of cardiopulmonary bypass without hypothermia in this study. Atrial septal fenestration was performed in 8 patients. In one patient, bi-directional cardiopulmonary procedure was performed 2 years before Fontan operation.</p><p><b>RESULTS</b>There was one early death caused by acute hepatic function failure and one late death caused by repeated lung infections. The follow-up of 1 to 4.5 years showed that all patients' cardiac functions were grade I to II, and arterial oxygen saturation was 92% - 96%.</p><p><b>CONCLUSIONS</b>The early and mid-term outcome of Fontan operation with extracardiac conduit on beating hearts is good and the method can be used in the single ventricle repair.</p>