心室压力超负荷早期心肌纤维化的动态病理学变化

目的 通过主动脉弓缩窄建立小鼠心室压力超负荷模型,探讨在心室压力超负荷早期心肌纤维化的动态病理学变化.方法 选用10周龄、体质量23 ～ 25 g的雄性C57BL/6J小鼠40只,随机分为4组(n=10):(①假手术组(SHAM组)、②缩窄3d组(TAC3D组)、③缩窄7d组(TAC7D组)、④缩窄14 d组(TAC14D组).各缩窄组小鼠行主动脉弓缩窄术,假手术组除不缩窄主动脉弓部,其他操作同各缩窄组.心脏导管检测小鼠心脏功能变化情况;采用心脏体质量比、心肌细胞直径大小等指标评价小鼠心肌结构代偿性变化情况;Masson染色观察小鼠心肌纤维化变化情况.结果 ①与假手术组相比,各缩窄组射血分数无显著改变(P＞0.05);②与假手术组相比,各缩窄组心体比显著增加,心肌细胞直径显著增大[SHAM组、TAC3D组、TAC7D组、TAC14D组心肌细胞直径依次为(13.56 ±0.24)、(18.02±0.52)、(18.76±0.96)、(21.20±1.85) μm,P＜0.05].③与假手术组相比,各缩窄组心肌管周纤维化程度显著增加,且随缩窄时间延长而加重[SHAM组、TAC3D组、TAC7D组、TAC14D组血管周围纤维化面积与血管面积比依次为(0.18±0.02)、(0.37±0.02)、(1.22±0.08)、(2.05±0.12),P＜0.05].结论 在心室压力超负荷早期,心肌纤维化主要出现于血管周围,且纤维化程度随缩窄时间延长而逐渐加重.

Dynamic pathological changes of myocardial fibrosis in mice in an early stage of ventricular pressure overload

Objective To investigate the dynamic pathological changes of myocardial fibrosis in an early stage of ventricular pressure overload in a mouse model of transverse aortic constriction (TAC).Methods Forty male C57BL/6J mice were randomly divided into the sham-operated group and 3 TAC groups for observation at 3,7,and 14 d after TAC (TAC3D,TAC7D and TAC14D groups,respectively).Cardiac function of the mice was examined with cardiac catheter measurement.The myocardial structure changes were evaluated based on the heart weight index and the myocardial cell diameter,and the changes in the myocardial fibers were observed with the Masson staining.Results Compared with those in the sham-operated group,the mice in the TAC groups showed no significant changes in the ejection fraction (P ＞ 0.05),but the heartto-body weight ratio and myocyte width were increased obviously (the myocyte width in sham,TAC3D,TAC7D and TAC14D groups was 13.56 ± 0.24,18.02 ± 0.52,18.76 ± 0.96,and 21.20 ± 1.85 μm,respectively,P ＜ 0.05).Compared with that in the sham-operated group,the severity of perivascular fibrosis increased significantly in the TAC groups and exacerbated as the TAC time extended (the perivascular fibrosis area/vascular area ratios in the 4 groups were 0.18 ± 0.02,0.37 ± 0.02,1.22 ± 0.08,and 2.05 ± 0.12,respectively,P ＜ 0.05).Conclusion Perivascular fibrosis is the major pathological finding in the early stage of ventricular pressure overload in mice and deteriorates progressively with the extension of TAC time.