Effects of Exercise Rehabilitation on Cardiac Fibrosis and Function in Rats with Myocardial Infarction
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摘要:
目的 探究运动康复对心肌梗死大鼠心脏纤维化及心功能的影响。 方法 24只雄性SD大鼠随机分为4组：心肌梗死运动组（MI-E组）、心肌梗死不运动组（MI-Sed组）、假手术运动组（Sham-E组）、假手术不运动组（Sham-Sed组），每组5～7只。采用结扎左冠状动脉前降支（LAD）制备心肌梗死模型，而假手术组只穿针不结扎。术后1周开始运动训练，包括适应性运动1周和正式运动4周，而不运动组全程不参加运动训练。运动结束后行超声心动图检查，HE、Masson和Tunel染色，以及透射电镜检测。 结果 与Sham组比较，MI组左心室室壁变薄及收缩功能降低，以MI-Sed组明显（P < 0.05）；而MI-E组与MI-Sed组比较，LVESD、LVEF和FS有所改善（P < 0.05）；Sham-E组与Sham-Sed组比较差异无统计学意义（P > 0.05）。HE染色显示与Sham组比较，MI组心肌细胞呈现不同程度溶解，伴炎性细胞浸润，成纤维细胞增生，而MI-E组损伤较轻。Masson染色显示MI组较Sham组心肌细胞排列紊乱，心肌纤维化明显增加，而MI-E组与MI-Sed组、Sham-E组与Sham-Sed组相比较，胶原容积分数（CVF%）降低（P < 0.05）。Tunel染色显示MI组较Sham组心肌细胞凋亡数增多，而MI-E组与MI-Sed组、Sham-E组与Sham-Sed组相比较，心肌细胞凋亡指数降低（P < 0.05）。透射电镜显示MI组较Sham组心肌细胞及线粒体损伤严重，肌纤维疏松紊乱，而MI-E组较MI-Sed组心肌细胞损伤较轻，线粒体结构较完整，自噬小体形成较多。 结论 运动康复可减少MI大鼠的心肌细胞损伤和细胞凋亡，减少心肌梗死面积，改善心肌纤维化及心功能；运动可适度诱导自噬水平发挥心脏保护作用。 Abstract:Objective To explore the effect of exercise rehabilitation on cardiac fibrosis and function in rats with myocardial infarction. Methods Twenty-four male SD rats were randomly divided into four groups: MI-E group, MI-Sed group, Sham-E group and Sham-Sed group, with five to seven rats in each group. A myocardial infarction model was prepared using ligation of the left anterior descending coronary artery （LAD）, while the sham surgery group underwent needle insertion without ligation. One week after surgery, exercise training was initiated, including one week of adaptive exercise and four weeks of formal exercise. The non-exercise group did not participate in any exercise training throughout the study. After completion of the exercise regimen, echocardiography, HE staining, Masson staining, Tenel staining, and transmission electron microscopy were performed for evaluation. Results Compared with sham group, left ventricular wall thinning and systolic function were decreased in MI groups, especially in MI-Sed group （P < 0.05）, while LVESD, LVEF and FS were improved in MI-E group compared with MI-Sed group （P < 0.05）; there was no significant difference between Sham-E group and Sham-Sed group （P > 0.05）. Compared with the sham group, HE staining showed that cardiomyocyte exhibited different degrees of lysis with inflammatory cell infiltration and fibroblast proliferation in the MI group while the damage was milder in the MI-E group. Masson staining showed that cardiomyocyte was disorganized and myocardial fibrosis was significantly increased in the MI group compared with the sham group, while collagen volume fraction （CVF%） was decreased in the MI-E group compared with the MI-Sed group and the Sham-E group compared with the Sham-Sed group （P < 0.05）. Tunel staining showed that compared with the Sham group, the MI group had increased myocardial cell apoptosis, while the MI-E group had a lower myocardial cell apoptosis index compared to the MI-Sed group, Sham-E group, and Sham-Sed group （P < 0.05）. Transmission electron microscopy showed that compared with the Sham group, the MI group had severe damage to myocardial cells and mitochondria, as well as loose and disordered muscle fibers, while the MI-E group had milder myocardial cell injury, more intact mitochondrial structure, and more formation of autophagosomes. Conclusion Exercise rehabilitation can reduce cardiomyocyte damage and apoptosis, reduce myocardial infarct area, improve myocardial fibrosis and cardiac function in MI rats. Exercise can moderately induce autophagy level to play a cardioprotective role. -
Key words:
- Myocardial infarction /
- Exercise rehabilitation /
- Autophagy /
- Myocardial fibrosis
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图 1 心脏组织HE染色（×400）
A：MI-E组；B：MI-Sed组；C：Sham-E组；D：Sham-Sed组。
Figure 1. HE staining of heart tissue （×400）
图 2 心脏组织Masson染色（×400）和CVF%
A：MI-E组；B：MI-Sed组；C：Sham-E组；D：Sham-Sed组。与MI-E组比较，*P < 0.05；与MI-Sed组比较，#P < 0.05；与Sham-E组比较，+P < 0.05。
Figure 2. Masson staining of heart tissue（×400）and CVF%
图 3 心脏组织Tunel染色（×400）
A：MI-E组；B：MI-Sed组；C：Sham-E组；D：Sham-Sed组。
Figure 3. Tunel staining of heart tissue （×400）
图 4 心脏组织透射电镜检测
a：MI组；b：Sham组，a～b为2 μm电镜图。A：MI-E组；B：MI-Sed组；C：Sham-E组；D：Sham-Sed组。A～D为1 μm电镜图。红色箭头表示自噬小体。
Figure 4. Transmission election microscope detection of heart tissue
表 1 4组大鼠超声心动图指标（
$ \bar x \pm s $ ）Table 1. Parameters of echocardiography in four groups of rats （
$ \bar x \pm s $ ）指标 MI-E组（n = 6） MI-Sed组（n = 7） Sham-E组（n = 6） Sham-Sed组（n = 5） F P AWTd （mm） 1.48 ± 0.30 1.23 ± 0.15 2.05 ± 0.34*# 1.82 ± 0.26*# 11.613 < 0.001a AWTs （mm） 1.94 ± 0.30 1.57 ± 0.19 2.64 ± 0.49*# 2.46 ± 0.25*# 14.398 < 0.001a PWTd （mm） 2.16 ± 0.24 1.87 ± 0.27 2.51 ± 0.51# 2.37 ± 0.25# 4.256 0.018a PWTs （mm） 3.02 ± 0.52 2.55 ± 0.34 3.38 ± 0.56# 3.29 ± 0.11# 4.865 0.011a LVEDD （mm） 6.55 ± 0.84 6.88 ± 0.95 6.02 ± 0.31# 5.85 ± 0.53# 2.574 0.083 LVESD （mm） 4.53 ± 0.67 5.52 ± 0.51* 3.50 ± 0.60*# 3.42 ± 0.24*# 14.726 < 0.001a LVEF （%） 58.99 ± 7.60 45.55 ± 3.41* 70.96 ± 7.54*# 70.17 ± 7.08*# 21.368 < 0.001a FS 30.82 ± 6.60 20.00 ± 2.52* 42.10 ± 8.10*# 41.12 ± 6.84*# 17.583 < 0.001a 组间比较，aP < 0.05；与MI-E组比较，*P < 0.05；与MI-Sed组比较，#P < 0.05。 
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表 2 4组大鼠细胞凋亡指数[（
$ \bar x \pm s $ ），%]Table 2. Apoptosis index in four groups of rats [（
$ \bar x \pm s $ ），%]组别 n 细胞凋亡指数 MI-E组 6 14.00 ± 1.98 MI-Sed组 7 29.85 ± 4.47* Sham-E组 6 1.89 ± 0.14*# Sham-Sed组 5 4.82 ± 2.07*#+ F 41.39 P < 0.001a 组间比较，aP < 0.05；与MI-E组比较，*P < 0.05；与MI-Sed组比较，#P < 0.05；与Sham-E组比较，+P < 0.05。
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