| Objective:Current studies suggest that atrial remodeling is one of the mechanisms for the generation and maintenance of atrial fibrillation（AF）.Galectin-3（Gal-3）has effects on pro-inflammatory and pro-fibrotic,which may cause atrial remodeling.The aim of this study was to investigate the effect of gal-3 on induction of AF in the pathological state of Diabetes Mellitus（DM）and the intervention effect of modified citrus pectin（MCP）as an inhibitor on atrial remodeling.Methods:A total of 72 healthy rabbits were randomly divided into three groups:normal control group（CN,n=24）,diabetes mellitus group（DM,n=24）,DM+Gal-3inhibitor group（MCP,400mg/day/kg,n=24）.After 8 weeks of housing under the same conditions,the weight,blood glucose and other basic indicators of the rabbits were measured.（1）Echocardiogram indexes were comprised of the data collected in echocardiography.（2）Isolated heart electrophysiology technique was used to obtain electrophysiological parameters and AF inducibility stimulated by the burst pacing.（3）Confocal microscopy and fluorescence staining technique were used to analyze the intracellular calcium transients in atrial myocytes.（4）Isolating atrial myocytes through Langendorff system and the whole-cell inward ICa,La,L was recorded with patch-clamp technique.（5）HE staining and Masson staining were used to evaluate the morphology and interstitial collagen deposition in right atrial tissues.（6）The protein expression levels of inflammatory and fibrosis-related factors in left atrial tissue were confirmed by Western Blotting.Results:（1）Compared with the CN group,LAD in the DM group significantly increased（P<0.01）,and IVS as well as PWT in the DM group significantly increased（P<0.01）.Compared with the DM group,MCP group LAD in the DM group significantly decreased（P<0.01）,and IVS as well as PWT significantly decreased（P<0.01）.Pairwise comparison of other echocardiographic parameters among the three groups showed no statistical significance（P>0.05）.（2）Compared with the CN group,IACT and AERPD of the DM group had significantly prolonged（P<0.01）,and the incidence of AF significantly increased（126/160 vs.5/160,P<0.01）.Compared with the DM group,IACT and AERPD of the DM group had significantly shortened（P<0.01）,and the incidence of AF significantly reduced（30/160 vs.126/160,P<0.01）.Pairwise comparison between the three groups of SCL and AVWCL showed no statistical significance（P>0.05）.（3）Compared with the CN group,the calcium mean fluorescence intensity in atrial myocytes of the DM group significantly increased（2.18±0.26 vs.1.60±0.14,P<0.01）,while that of the MCP group significantly decreased（1.69±0.22 vs.2.18±0.26,P<0.01）.（4）Compared with the CN group,the ICa,La,L maximum current density of atrial myocytes in the DM group was significantly increased（7.05±1.32 vs.4.22±1.48,P<0.01）,while the ICa,La,L maximum current density of atrial myocytes in the MCP group was significantly decreased（5.26±1.29 vs.7.05±1.32,P<0.01）.（5）Compared with the CN group,the representative photomicrographs of HE staining and Masson staining indicated the disorders in arrangement of atrial myocytes in DM group,and atrial interstitial fibrosis in DM group was significantly higher（P<0.01）.Compared with the DM group,the arrangement of atrial myocytes of the MCP group were consistent and atrial interstitial fibrosis was significantly reduce（P<0.01）.（6）Compared with the CN group,the protein expression levels of inflammatory and fibrosis-related factors in left atrial tissue of the DM group were significantly up-regulated（P<0.05）,while that of the MCP group were significantly decreased（P<0.05）.Conclusion:Galectin-3 inhibitor MCP has antagonistic effect on atrial inflammation and fibrosis,limits the occurrence and progress of electric remodeling,structure remodeling and ion channel remodeling of atrium in DM rabbits,and reduces the induction rate of AF,which may exploits new ideas for upstream prevention and treatment of DM related AF. |
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