| 其他摘要 | Cathelicidins are a family of antimicrobial peptides acting as multifunctional effector molecules of innate immunity, which are firstly found in mammalians. Cathelicidins have conserved structures. Cathelicidins consist of an N-terminal putative signal peptide, a conserved cathelin-like domain, and a C-terminal antimicrobial domain that varies remarkably in size (ranging from 12 to 100 amino acids) . C-terminal cationic antimicrobial domain that becomes active after being released from the N-terminal cathelin portion of the holoprotein. They possess broad spectrum antimicrobial activity, not only against Gram-positive bacteria, Gram-negtive bacteria, fungi, and viruses, but also many antibiotic-resisted clinical bacteria. In addition, they possess many other biological activities, such as immune cell chemotaxis, mast cell degranulation, and histamine release, transcriptional regulation of macrophages, wound repairing, angiogenesis, cytolytic activity, etc. In this thesis, a series of experiments were carried out to study goat cathelicidin (GC) antimicrobial peptide family from Capra hirca. We analyzed the structure of GC, predicted and synthesized the mature peptide. The possible biological activities of GC were invesitigated. It is microbicidal against Gram-negtive bacteria and fungi, including many antibiotic-resisted clinical bacteria, but not obvious to Gram-positive bacteria. GC had the activity to scavenge ABTS+ radical. GC exhibited no hemolytic activity, lectin-like activity, and serine protease inhibitory activity. According to the results of bacteria killing kinetics experiment, circular dichroism spectroscopy (CD) and scaning electron microscopy (SEM), we deduced that GC attached to microbial plasma membrane through electrostatic interaction, changed the conformation, leaded to microbial plasma membranes retraction and induced the death of bacteria cells. In vitro and in vivo experiments were carried out for pharmacological and pharmacodynamic study of GC. GC exhibited good stability in human normal serum. A certain concentration of salt could increased GC’s antimicrobial activity. Animal model experiments showed that GC possessed effective therapeutic effects against mice vaginitis infection induced by candida albicans. The characteristics of GC and its therapeutic efficacy demonstrated by animal model experiments make it an excellent template for the development of topical antibiotics. |
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