Expression And Significance Of CyPA，CD147，MMP-2and MMP-9in Cyclospoirn-induced Gingival Overgrowth Of Rat

Objective:To establish the animal model of Cyclosporin-induced gingival overgrowth (CIGO).Using immunohistochemistry and Western blot methods to detect the expressions of CyPA,EMMPRIN (CD147), MMP-2, MMP-9in the overgrowth gingival tissues, so as toinvestigate the pathogenesis of Cyclosporin-induced gingival overgrowth (CIGO).Methods:1.48male Sprague-Dawley rats were randomly divided into CsAgroup and controlgroup. Rats from experimental group were subcutaneous injected with CsA, based on theiractual body weights, castor oil for the control group rats. Observation gingival hyperplasiaof each rat weekly after the beginning of injection.2. All of the rats were sacrified after injected everyday for4weeks. Evaluated theresorption of alveolar bone by Micro-CT.3. Excised the gingival tissues around the bilateral maxillary and mandible molarsfrom each rat, and analyzed with histological examination.4. Immunohistochemistry was applied for location and detection the expressions ofCyPA, CD147, MMP-2, MMP-9between CsAgroup and control group.5. Western blot was used to quantify the expressions of CyPA, CD147, MMP-2,MMP-9between CsAgroup and control group.Results:1. Gross observation：after injected for2weeks, the gingival tissues of CsAgrouprats began to appear hyperplasia. After4weeks continuously injected, the gingival tissuesbecame spherical and nodular hyperplasia, papillae gingiva overgrowth, gingival sulcusdeepened, false periodontal pocket formed. Periodontium examination revealed nobleeding and periodontal attachment loss. To conclude, CIGO animal model wassuccessfully established.2. Micro CT examination: both the CsAgroup and control group show the intactalveolar bone structure with no resorption.3. Western blot revealed that CyPA, MMP-2, MMP-9expressions were dramaticallydecreased in CsAgroup as compared to control group. However, CD147did not showstatistic difference.4. Immunohistochemistry showed that CyPA, MMP-2, MMP-9expressions were significantly decreased in CsAgroup as compared to control group (P<0.01). However,CD147did not show statistic difference (P＞0.05).Conclusions:CyclosporineA down regulates the expression of CyPA, influencing CyPA–CD147interaction, inhibiting the signaling pathway of matrix metalloproteinases secretin,inducing the imbalanced metabolism of collagen, which may contribute to the pathogenesisof CIGO.