Study On The Proinflammatory Effect Of Metalloproteinase In Jellyfish Nemopilema Nomurai Nematocyst Venom

In recent years,with the changes of marine environment and the impact of human production and life,the phenomenon of jellyfish bloom around the world has occurred frequently.Jellyfish dermatitis is the main clinical response after jellyfish stings.The inflammatory response accompanied by the entire process of jellyfish dermatitis,seriously affecting people's daily life and health.Due to the complexity and variety of jellyfish venom,there has been no effective drug for the treatment of jellyfish dermatitis.The transcriptomics and proteomics of jellyfish venom show that there are abundant metalloproteinases in jellyfish venom.Metalloproteinases play an important role in the venom of terrestrial animals according to the previous reports.Therefore,in this thesis,the biological effects of metalloproteinases on jellyfish dermatitis were studied in vitro and in vivo by matrix metalloproteinase inhibitors to inhibit the inflammation,respectively.The main results are as follows:1.NnNV can significantly reduce cell survival and induce cell death by promoting cell apoptosis according to the results of studies in vitro.When the NnNV acts on two kinds of skin cells and two kinds of inflammatory model cells,the gene expression and protein expression levels of IL-6,MCP-1 and TNF-a in cells are significantly increased,indicating that NnNV can stimulate cells produced inflammation.The metalloproteinase inhibitors BMT and EDTA can significantly reduce the toxicity of NnNV to cells,improve the survival rate of cells,and significantly reduce the content of inflammatory factors in cells.It is indicated that the metalloproteinase in the NnNV plays an important role in the process of inflammation.2.NnNV could stimulate the expression of two inflammatory cells,lymphocyte and leukocyte,and three inflammatory factors,IL-6,MCP-1 and TNF-a in mice according to the results of studies in vivo.Skin histopathological sections showed that NnNV had an effect on inflammatory cells,and the content of inflammatory cells in mice skin decreased significantly when metalloproteinase inhibitor acted.Afterwards,the content of inflammatory cells in skin tissue decreased,indicating that metalloproteinases in NnNV have an inflammatory effect.3.The results of muscle toxicity test of NnNV showed that NnNV could increase the activity of lactate dehydrogenase and creatine kinase in vivo,which might cause muscle tissue injury.However,the activity of lactate dehydrogenase and creatine kinase decreased significantly after the action of metalloproteinase inhibitor,which indicated that metalloproteinase played an important role in the myotoxicity of NnNV.