| Background: Diabetes mellitus(DM) is one of the independent risk factors for atrial fibrillation(AF), and the potential mechanisms of diabetes related AF is not clear. Previous studies have indicated that inflammation and oxidative stress play an important role in the development of diabetes and atrial fibrillation. It is speculated that inflammation and oxidative stress may be the potential mechanism of diabetes related atrial fibrillation.Objective:To explore the mechanisms of diabetes related atrial fibrillation, and antioxidant and anti-inflammatory agent xanthine oxidase inhibitor(allopurinol) on diabetic atrial remodeling. From the different levels to explore the potential mechanisms diabetic atrial structural remodeling and electrical remodeling and evaluate the protective effects of allopurinol.Methods: Our experiment consists of three parts, each part of the application of health adult Japanese rabbits(n=30), randomly divided to three groups: control group(control, C group), diabetes mellitus group(DM group), diabetes in the allopurinol group(ALL group)(n=10). The diabetic model was established by 120mg/kg injection in the ear margin vein of rabbits. ALL group was treated with 50mg/d, and the other group was fed for 8 weeks. 8 weeks later, we established Langendorff perfused rabbit heart model, measuring the interatrial conduction time(IACT), the atrial effective refractory period(AERP), AERP dispersion(AERPD), the application of Burst stimuli to induce atrial fibrillation. Serum superoxide dismutase(SOD), malondialdehyde(MDA) and myeloperoxidase(MPO) levels were measured. Pathological examination including hematoxylin and eosin(HE) staining and Masson staining to observe the atrial myocardial cross-sectional area and atrial fibrosis. Western Blotting analysis to study the changes of ERK, P38, JNK and TGF- β protein and phosphorylation expression in the three groups.Results:Compared with control group, the MDA level in diabetes was significantly increased(P<0.05), SOD level in allopurinol group was significantly increased(P<0.05); The heart weight/body weight ratio of rabbits in DM and ALL group were significantly higher in diabetic group(P<0.05), IACT(P<0.05) significantly prolonged. AF inducibility in diabetic group was increased compared with controls(2.22% vs 30.37%, P <0.05); HE staining showed that the diabetic group cell disorder, atrial myocyte cross-sectional area increase(11938.57±7554.66μm~2 vs 18509.37±1917.60μm~2, P>0.05), Pathological examination showed that the collagen volume fraction was significantly increased in diabetic group(1.90±0.33% vs 6.83±1.43%, P<0.05); NF-κB, TGF-β, P-P38,MMP2,MMP9 expression increased significantly in DM group(P <0.05). Compared with DM group, heart weight/rabbit weight in allopurinol group was relatively low(P < 0.05). and AF inducibility in allopurinol group was significantly reduced(30.37% vs 8.15%, P < 0.05); Atrial myocardial cross sectional area was reduced in allopurinol group compared with DM group(18509.37±1917.60μm~2 vs 15818.47±644.58μm~2, P > 0.05), collagen volume fraction decreases compared with DM group(6.83±1.43% vs 4.86±1.18%, P<0.05); NF-κB, TGF-β, P-P38,MMP2,MMP9 expression in ALL group were significantly decreased(P < 0.05).Conclusion: 1) Xanthine oxidase activation and oxidative stress play important role in atrial electrical and structural remodeling, and AF promotion; 2) Through anti-inflammatory and anti-oxidative effects, xanthine oxidase inhibitor allopurinol could alleviate diabetes related inflammation and oxidative stress, attenuate atrial electrical and structural remodeling and reduce the inducibility of AF. |
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