秋水仙碱对实验性克氏锥虫病引起的心肌损伤的影响。

Effect of colchicine on myocardial injury induced by Trypanosoma cruzi in experimental Chagas disease.

机构信息

Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina da, Universidade de São Paulo, São Paulo, Brazil.

出版信息

J Card Fail. 2012 Aug;18(8):654-9. doi: 10.1016/j.cardfail.2012.06.419.

DOI:10.1016/j.cardfail.2012.06.419

PMID:22858082

Abstract

BACKGROUND

The hallmark of Chagas disease (CD) is multifocal myocarditis and extensive fibrosis. We investigated the potential effect of colchicine on myocardial remodeling in experimental CD.

METHODS AND RESULTS

One hundred Syrian hamsters were randomly divided into noninfected untreated control (CG), noninfected control treated with colchicine (COLG 0.4 mg kg(-1) d(-1) by gavage), infected (IG), and infected treated with colchicine (ICOLG, 0.4 mg kg(-1) d(-1)) groups. The interstitial collagen volume fraction (ICVF) was evaluated by videomorphometry with picrosirius red staining. The gelatinolytic activities of matrix metalloproteinase (MMP) 2 were examined with the use of zymography. Myocarditis was described according to the Dallas criteria. Statistical comparisons were performed with parametric analysis of variance and Tukey test. ICVF (%) accumulation was attenuated in infected colchicine-treated animals in the left (CG 0.81 ± 0.13, COLG 0.85 ± 0.13, IG: 1.35 ± 0.31,* ICOLG 1.06 ± 0.19; P < .05 compared with ICOLG) and right ventricles (CG 1.4 ± 0.36, COLG 1.26 ± 0.14, IG 1.97 ± 0.058, ICOLG: 1.52 ± 0.23; P < .05 compared with ICOLG). A significant increase in MMP-2 enzymatic activity (UA) was observed in ICOLG (17,432.8) compared with GC (3731.6), COLG (2,792.6), and IG (4,286.3; *P < .001). In IG, 66% of animals had myocarditis compared with only 49% in ICOLG.

CONCLUSIONS

Colchicine had a protective effect on myocardium, indicated by decreased interstitial myocardial fibrosis, increased intensity of MMP-2, and attenuated myocardial inflammation.

摘要

背景

恰加斯病（CD）的标志是多灶性心肌炎和广泛纤维化。我们研究了秋水仙碱对实验性 CD 心肌重构的潜在影响。

方法和结果

100 只叙利亚仓鼠被随机分为未感染未治疗对照组（CG）、未感染秋水仙碱治疗对照组（CG 给予秋水仙碱 0.4mg/kg/d 灌胃）、感染组（IG）和感染秋水仙碱治疗组（ICOLG，0.4mg/kg/d）。通过视频形态计量学和苦味酸天狼星红染色评估间质胶原容积分数（ICVF）。使用明胶酶谱法检测基质金属蛋白酶（MMP）2 的凝胶酶活性。根据达拉斯标准描述心肌炎。采用方差分析和 Tukey 检验进行统计学比较。感染秋水仙碱治疗的动物左心室（CG 0.81±0.13，COLG 0.85±0.13，IG：1.35±0.31，*ICOLG 1.06±0.19；*P<0.05 与 ICOLG 相比）和右心室（CG 1.4±0.36，COLG 1.26±0.14，IG 1.97±0.058，*ICOLG：1.52±0.23；P<0.05 与 ICOLG 相比）的 ICVF（%）积累减少。与 GC（3731.6）、COLG（2792.6）和 IG（4286.3）相比，ICOLG 中 MMP-2 酶活性（UA）显著增加（17432.8）。IG 中 66%的动物发生心肌炎，而 ICOLG 中只有 49%。