Investigation of the therapeutic potential and protective mechanism of melatonin treatment in the mouse infection model of influenza A H1N1 virus

Autor: Li-Ge Shi, 施力格
Rok vydání: 2014
Druh dokumentu: 學位論文 ; thesis
Popis: 102
Objectives: To investigate the therapeutic potential and protective mechanism of melatonin treatment in the mouse infection model of influenza A H1N1 virus. Backgrounds: Influenza, commonly known as flu, is an infectious disease caused by RNA virus of the Orthomyxoviridae family that affects birds and mammals. It is a leading cause of morbidity, mortality and economic loss worldwide. The inflammatory response to influenza virus is crucial for the clearance of virus, however, uncontrolled inflammatory response in the lungs also leads to severe pneumonia. Furthermore, reactive oxygen species (ROS) are produced in the lung under infection and subsequently increase local inflammation and thus contribute to pulmonary tissue damage. The anti-inflammation and anti-oxidation effects of melatonin may provide a benefit for this disease. Materials and Methods: In this study, we generated two of the influenza virus strains, A/PR/8/34 (H1N1) and WSN, by using reverse genetics technique, and further infected Balb/c or C57BL/6 mice with these viruses. To investigate the protective mechanism of melatonin in this model by using reverse transcription PCR(RT-PCR) and Enzyme-Linked Immunosorbent Assay(ELISA) for the evaluation of antioxidative enzymes, inflammatory cytokines and chemokines in the lungs of experimental mice. Results: Our results demonstrated that melatonin treatment improved the survival of experimental mice. The severity of influenza virus induced pneumonia in experimental mice was decreased under melatonin trearment. In addition, melatonin treatment significantly reduced the expression of anti-oxidant enzymes, Heme oxygenase-1 (HO-1) and Copper Superoxide Dismutase (CuSOD). Furthermore, the decrease of inflammatory cytokine, TNF-α, and the increase of anti-inflamatory cytokine, IL-10 and IL-6, were observed in lymphocyte from BALF in our experimental mice. Conclusion: Our data demonstrated that melatonin treatment exhibits a therapeutic effect in influenza A virus-infected mouse model by elevating the antioxidant enzyme levels. The results of this study could be the theoretical basis of the therapeutic potential of melatonin in severe influenza A H1N1 virus infection.
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