sinomenine and Chronic-Disease

BACKGROUND In the present study, we aimed to investigate the effects of sinomenine (SIN) on chronic intermittent hypoxia (CIH)- induced lung injury in rats, and to explore the underlying mechanisms. MATERIAL AND METHODS To perform the investigation, a CIH rat model was established. ELISA assay was applied to detect the level of inflammatory cytokines. Oxidative stress bio-markers (MDA, SOD, and CAT) were determined in lung tissues. In addition, the expression level of NADPH oxidase 2 (Nox2) was analyzed by Western blotting and qRT-PCR, respectively. RESULTS The results showed that compared with other groups, more obvious pulmonary pathological changes were observed in the CIH group. The level of inflammatory cytokines in the CIH group was markedly higher than that in the control and Con-S groups. Compared with the control and Con-S groups, oxidative stress was notably increased in the CIH group. Expression of Nox2 was also increased in the CIH group. The effects caused by CIH in rats were attenuated by SIN treatment. CONCLUSIONS SIN can reverse chronic intermittent hypoxia-induced lung injury through inhibiting inflammation and oxidative stress.

Topics: Animals; Chronic Disease; Cytokines; Down-Regulation; Hypoxia; Inflammation; Inflammation Mediators; Lung; Lung Injury; Male; Mice; Morphinans; NADPH Oxidases; NF-E2-Related Factor 2; Oxidative Stress; Rats, Sprague-Dawley; Signal Transduction

Chronic rejection (CR) with graft vasculopathy is recognized as a major cause of graft loss over time. Sinomenine (SN) has anti-inflammatory, antirheumatic, and immunomodulatory effects. Previously, we demonstrated antimacrophage and anti-T cell effects of SN in acute rejection. In the current study, we investigated the effect of SN in a rat cardiac allograft model of CR.. After a brief course of cyclosporine A (CsA), Lewis recipients of F344 hearts were treated with SN alone, CsA alone, or a combination of both drugs. Grafts were analyzed morphometrically and by immunohistochemistry. Expression of basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and endothelin 1 was assessed by reverse transcription-polymerase chain reaction. Antidonor IgM formation was investigated by FACS.. Cardiac grafts from SN-treated rats showed less pronounced vasculopathy in comparison with untreated rats or CsA-treated recipients. After treatment with a combination of both drugs, rats had significantly less graft vasculopathy than rats receiving either drug alone. Treatment with CsA alone led to a decrease in bFGF expression, whereas SN alone did not affect gene expression. SN in combination with CsA, however, markedly reduced expression of bFGF, vascular endothelial growth factor, and endothelin 1. SN alone did not inhibit antidonor antibody formation.. These studies demonstrate for the first time the therapeutic value of SN in a model of chronic cardiac allograft rejection. SN in combination with low-dose T cell-targeted immunosuppression is effective in controlling tissue remodeling in the context of CR and is associated with inhibition of intragraft expression of mediators involved in angiogenesis, vascular tone, and tissue remodeling.

Topics: Adjuvants, Immunologic; Animals; Antibody Formation; Chronic Disease; Cyclosporine; Cytokines; Drug Therapy, Combination; Graft Rejection; Growth Substances; Heart; Heart Transplantation; Immunosuppressive Agents; Male; Morphinans; Myocardium; Rats; Rats, Inbred F344; Transplantation, Homologous; Ventricular Remodeling