ABSTRACT
OBJECTIVE: To explore a new method of establishing acute myocardial infarction model in diabetic miniature pigs through video-assisted thoracoscopic surgery (VATS). METHODS: Seven normal miniature pigs and 7 diabetic miniature pigs underwent VATS by selectively ligating left anterior descending coronary artery and then were evaluated through serology, imaging and histology. RESULTS: The serum levels of troponin (cTni) and myoglobin (MYO) in both groups significantly increased by over 10 folds of upper normal limit after VATS. Echocardiography, MRI and histopathologic analysis showed that the affected myocardial parts were apex, left ventricular wall and interventricular septum cosco section. But heart function of diabetic miniature pigs were relatively lower; infarction area/area-at-risk ratio higher (18.4% ± 5.5% vs 5.3% ± 3.9%, P = 0.03) , myocardial infarction through-wall degree more severe. These were in accordance with poor ischemic tolerance in diabetic myocardia. CONCLUSION: VATS is a safe and effective method for establishing AMI model in diabetic miniature pigs.
Subject(s)
Disease Models, Animal , Myocardial Infarction , Thoracic Surgery, Video-Assisted , Animals , Diabetes Mellitus, Experimental , Male , Swine , Swine, MiniatureABSTRACT
AIM: It is well known that neural stem/progenitor cells (NS/PC) are an ideal cell type for the treatment of central nervous system (CNS) disease. However, ethical problems have severely hampered fetal NS/PC from being widely used as a source for stem cell therapy. Recently, it has been demonstrated that autologous bone marrow mesenchymal stem cells (BMSC) can transdifferentiate into neural progenitor cells (NPC). The biological function of BMSC derived NPC (MDNPC) in neuronal systems remains unknown. In the present study, we aimed to investigate whether MDNPC can promote in vitro neural regeneration, a process comprising mainly the generation of neurons and neurotransmitters. MAIN METHODS: We co-cultured BMSC, MDNPC or fetal NS/PC with PC12 cells and studied their roles on proliferation, neurite formation and dopamine release from PC12 cells. Furthermore, we also explored the mechanisms by which MDNPC regulate dopamine secretion from PC12 derived neural cells using Western blot. KEY FINDINGS: We found that both MDNPC and NS/PC had similar morphologies and there were no significant differences between MDNPC and NS/PC in promoting PC12 cell proliferation, neurite outgrowth, and dopamine release. We also demonstrated that NS/PC induced dopamine secretion was associated with an upregulation of dopamine transporter (DAT) levels. SIGNIFICANCE: In summary, MDNPC were comparable to NS/PC in promoting neural regeneration, indicating that MDNPC are a promising candidate source of neural stem cells for the treatment of neurological diseases.
Subject(s)
Bone Marrow Cells/metabolism , Mesenchymal Stem Cells/metabolism , Nerve Regeneration , Neural Stem Cells/metabolism , Neurons/metabolism , Animals , Blotting, Far-Western , Cell Proliferation , Dopamine/metabolism , Dopamine Plasma Membrane Transport Proteins/metabolism , Neurites/metabolism , PC12 Cells , Rats , Rats, Sprague-Dawley , Up-RegulationABSTRACT
BACKGROUND: The traditional Chinese medicine Tongxinluo can protect myocardium against ischaemia/reperfusion injury, but the mechanism of its action is not well documented. We examined the involvement of nitric oxide in the protective role of Tongxinluo. METHODS: Miniswine were randomized to four groups of seven: sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NNA, 10 mg/kg i.v.). Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively. RESULTS: Tongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA. CONCLUSIONS: Tongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase.