Topical Application of Calcium Antagonists for Inhibiting Tympanosclerosis in Guinea Pigs:A Preliminary Report

doi:10.3969/j.issn.1672-2922.2014.02.35

Abstract：Objective To discuss the preventive and therapeutical effects of calcium channel blockers in a guinea pig model of Tympanosclerosis. Methods An animal model of Tympanosclerosis was established by placing pathogenic bacteria in both ears of the guinea pigs. Drops of a calcium channel blocker, diltiazem, were added in the left ear to inhibit the secretion and chemotaxis activity of macrophages, thereby inhibiting bone morphogenetic protein-2 (BMP-2) expression and reducing calcium salt deposits, so as to prevent or delay the onset of tympanosclerosis (the experiment ear). Drops of 0.9% NS were placed in the right ear as the control. Observation targets included 1) inflammatory cells, granulation tissue and calcareous de-position in middle ear mucosa under an optical microscope;2) types of cells infiltrating the middle ear tissue and BMP-2 ex-pression demonstrated by CD68 and BMP-2 antibody;and 3) fibrocyte morphology changes, macrophage chemotaxis, fibrous hyperplasia and calcium salt deposits within the middle ear tissue near the tympanic membrane under a transmission electron microscope. Results Optical microscopy showed increased inflammation in experiment ears compared to the control. The muco-sae inside the bulla in both experiment and control ears showed high CD68 expression which was proportional with the severity of infection. BMP-2 staining in the mucosae of the control ear was significantly higher than that of the experiment ear, even when they showed similar levels of infection, clustering especially in the submucosa, possibly from macrophage agglomeration with increased secretion of BMP-2. Electron microscopy (TEM) in the experiment ear showed some columnar epithelial cells and only low grade fibrous hyperplasia, with infiltration of inflammatory cells, lymphocytes and a few macrophages but no calci-um salt deposits. In contrast, TEM in the control ear showed severe tissue damage, with hardly any recognizable normal tissue cells or structures and piles of macrophages filled with phagosomes in some areas, as well as significant fibrous hyperplasia and calcium salt deposits. Conclusion The study indicates that application of calcium antagonists in the middle ear can inhibit secretion and chemotaxic activities of the macrophage, reduce local inflammatory damage and thereby inhibit bone morphoge-netic protein-2 expression and calcium salt deposits, so as to prevent or delay the onset of tympanosclerosis.