高强度间歇训练对心肌梗死大鼠心脏结构和功能的影响

doi:10.12114/j.issn.1007-9572.2022.0292

中国全科医学 ›› 2022, Vol. 25 ›› Issue (33): 4159-4167.DOI: 10.12114/j.issn.1007-9572.2022.0292

所属专题：心血管最新文章合辑；心肌梗死最新文章合辑

高强度间歇训练对心肌梗死大鼠心脏结构和功能的影响

贾思琦¹, 王迪¹, 鲁燕², 贾永平²^,^*()

1.030000　山西省太原市，山西医科大学第一临床医学院
2.030000　山西省太原市，山西医科大学第一医院心血管内科

收稿日期:2022-05-05 修回日期:2022-06-22 出版日期:2022-11-20 发布日期:2022-08-11
通讯作者: 贾永平
贾思琦，王迪，鲁燕，等.高强度间歇训练对心肌梗死大鼠心脏结构和功能的影响[J].中国全科医学，2022，25（33）：4159-4167. [www.chinagp.net]
作者贡献：贾思琦参与设计研究方案，进行分子实验以及后期数据收集整理、统计分析并撰写草稿；王迪参与设计研究方案，进行动物造模、运动训练干预、取材及切片染色、数据收集整理；鲁燕负责文章的质量控制与审校；贾永平提出研究思路，对文章整体负责、监督管理。
基金资助:
山西省重点研发计划项目(201803D31092，201903D321180)

Effects of High-intensity Interval Training on Cardiac Structure and Function in a Rat Model of Myocardial Infarction

JIA Siqi¹, WANG Di¹, LU Yan², JIA Yongping²^,^*()

1.The First Clinical Medical College, Shanxi Medical University, Taiyuan 030000, China
2.Department of Cardiovascular Medicine, First Hospital of Shanxi Medical University, Taiyuan 030000, China

Received:2022-05-05 Revised:2022-06-22 Published:2022-11-20 Online:2022-08-11
Contact: JIA Yongping
About author:
JIA S Q, WANG D, LU Y, et al. Effects of high-intensity interval training on cardiac structure and function in a rat model of myocardial infarction [J]. Chinese General Practice, 2022, 25 (33) : 4159-4167.

摘要/Abstract

摘要： 背景高强度间歇训练（HIIT）作为心脏康复的运动方案之一，对于心肌梗死的作用还存在争议，且作用机制尚不明确。目的探讨HIIT对心肌梗死大鼠心脏结构和功能的影响。方法于2020年9月至2021年10月，随机选取3月龄雄性SD大鼠共78只，最终纳入研究56只。随机选取14只为假手术组（Sham组），其余大鼠制备急性心肌梗死（AMI）模型后随机分为心梗静息组（MI-SED组，n=14）、心梗HIIT组（MI-HIIT组，n=14），心梗中等强度持续训练（MICT）组（MI-MICT组，n=14）。Sham组与MI-SED组不进行训练，MI-HIIT组高强度与中等强度训练交替进行，MI-MICT组进行中等强度持续训练。AMI大鼠建模1周后MI-HIIT、MI-MICT组开始进行训练，训练4周后，四组分别随机取7只大鼠进行心脏超声检测，称量体质量（BW）、心脏质量（HW），计算心脏质量指数（HMI），检测血清肿瘤坏死因子α（TNF-α）水平，并取心脏组织进行HE染色、Masson染色及免疫组化分析；训练8周后对四组剩余7只大鼠采集数据和样本进行相同试验处理。结果训练4周后MI-HIIT组标准化HMI高于Sham组、MI-SED组和MI-MICT组（P<0.05）；训练8周后MI-HIIT组最终BW低于Sham组和MI-SED组，HW高于Sham组、MI-SED组和MI-MICT组，标准化HMI高于Sham组和MI-MICT组（P<0.05）。训练4周后，MI-HIIT组和MI-MICT组射血分数（EF）、缩短分数（FS）、左心室收缩末期后壁厚度（LVPWs）低于Sham组，高于MI-SED组（P<0.05）；MI-HIIT组和MI-MICT组左心室收缩末期内径（LVDs）低于MI-SED组（P<0.05）。训练8周后，MI-HIIT组EF、LVDs、左心室舒张末期内径（LVDd）、左心室收缩末期前壁厚度（LVAWs）高于Sham组和MI-SED组，FS、LVPWs高于MI-SED组（P<0.05）。HE染色显示，MI-HIIT组训练8周大鼠的心脏组织炎性病变较训练4周大鼠减轻，心肌细胞排列更紧密。Masson染色结果显示训练8周后MI-HIIT组、MI-MICT组心肌组织胶原纤维占比低于MI-SED组。免疫组化结果显示训练4、8周后MI-HIIT组、MI-MICT组心肌组织血管新生数高于Sham组、MI-SED组，训练8周后MI-HIIT组心肌组织血管新生数高于MI-MICT组。训练4周后，MI-HIIT组血清TNF-α高于MI-SED组；训练8周后，MI-HIIT组血清TNF-α水平高于MI-MICT组。结论 AMI早期进行HIIT，可提高HMI、诱导心肌组织早期炎性反应、减轻心肌纤维化、促进血管新生，改善心室重构，总体效果优于MICT。

关键词: 心肌梗死, 大鼠, 运动, 炎症, 心室重构, 心脏康复, 高强度间歇训练

Abstract:

Background

As one exercise program of cardiac rehabilitation, the role of high-intensity interval training (HIIT) in improving myocardial infarction is still controversial, and the mechanism is unclear.

Objective

To investigate the effect of HIIT on improving the cardiac structure and function in a rat model of myocardial infarction.

Methods

An experiment was conducted from September 2020 to October 2021. From a random sample of 78 3-month-old male SD rats, 56 were eventually included, and 14 of them were randomly selected as sham-surgery group (Sham group) , and the remaining 42 rats were equally randomized into MI-sedentary group (MI-SED group) , MI-HIIT group (MI-HIIT group) , and MI-medium-intensity continuous training (MI-MICT group) after being used for preparing a model of acute myocardial infarction (AMI) . Sham group and MI-SED group were not trained, MI-HIIT group received high-intensity and medium-intensity training alternately, MI-MICT group received medium-intensity continuous training. After 1 week of AMI modeling, MI-HIIT and MI-MICT groups received 8 weeks of training. At the end of 4 weeks of training, 7 rats in each of the 4 groups were randomly selected for detecting cardiac ultrasound, and weighing body weight, then were sacrificed, and their heart weight and serum tumor necrosis factor (TNF-α) were measured, cardiac mass index was calculated, and heart tissues were measured using H&E staining, Masson's Trichrome staining and immunohistochemical staining. At the end of 8 weeks of training, the same operation was performed on the remaining 7 rats in each of the groups.

Results

After 4 weeks of training, the standardized cardiac mass index of MI-HIIT group was higher than that of each of the other three groups (P<0.05) . The sham group had higher ejection fraction (EF) , fractional shortening (FS) and left ventricular end-systolic posterior wall thickness (LVPWs) than MI-HIIT and MI-MICT groups (P<0.05) . MI-SED group had lower EF, FS, and LVPWs, and higher left ventricular end-systolic diameter (LVESD) than MI-HIIT and MI-MICT groups (P<0.05) . After 8 weeks of training, MI-HIIT group had lower body weight than sham and MI-SED groups, higher heart weight than sham, MI-SED and MI-MICT groups, and higher standardized cardiac mass index than sham and MI-MICT groups (P<0.05) . MI-HIIT group demonstrated higher EF, LVESD, left ventricular end-diastolic diameter (LVEDD) , left ventricular end-systolic anterior wall thickness (LVAWs) than sham and MI-SED groups (P<0.05) . Moreover, MI-HIIT group also showed higher FS and LVPWs than MI-SED group (P<0.05) . HE staining results showed that MI-HIIT group had significantly improved inflammatory changes of heart tissue and more closely arranged myocardial cells at the end of the 8th week of training compared with at the end of 4 weeks of training. Masson's Trichrome staining results showed that after 8 weeks of training, the proportion of myocardial fibrillar collagen in myocardial tissues of MI-SED group was higher than that of MI-HIIT and MI-MICT groups. Immunohistochemical results showed that MI-HIIT group had more newly formed blood vessels in cardiac tissues than sham and MI-SED groups after 4 and 8 weeks of training, so did the MI-MICT group. The number of newly formed blood vessels in cardiac tissues of MI-HIIT group was more than that in MI-MICT group after 8 weeks of training. MI-HIIT group had higher serum TNF-α than MI-SED group after 4 weeks of training. After 8 weeks of training, the serum TNF-α in MI-HIIT group was higher than that in MI-MICT group.

Conclusion

HIIT performed in the early stage of AMI could improve cardiac mass index, induce early inflammatory response in myocardial tissue, reduce myocardial fibrosis, promote angiogenesis and ventricular remodeling. HIIT had better overall effect than MICT.

Key words: Myocardial infarction, Rats, Exercise, Inflammation, Ventricular remodeling, Cardiac rehabilitation, High-intensity interval training

贾思琦,王迪,鲁燕,等. 高强度间歇训练对心肌梗死大鼠心脏结构和功能的影响[J]. 中国全科医学, 2022, 25(33): 4159-4167. DOI: 10.12114/j.issn.1007-9572.2022.0292.
JIA Siqi,WANG Di,LU Yan, et al. Effects of High-intensity Interval Training on Cardiac Structure and Function in a Rat Model of Myocardial Infarction[J]. Chinese General Practice, 2022, 25(33): 4159-4167. DOI: 10.12114/j.issn.1007-9572.2022.0292.

图/表 12

表1 四组大鼠训练4周后BW、HW与标准化HMI比较（\d ±s）

Table 1 Comparison of body weight，heart weight and standardized cardiac mass index of four groups of rats at the end of 4 weeks of intervention

组别	只数	初始BW（g）	最终BW（g）	HW（g）	标准化HMI
Sham组	7	236.0±4.9	367.8±20.7	1.22±0.27	1.00±1.95
MI-SED组	7	236.3±4.8	354.8±34.5	1.37±0.19	1.18±0.20^a
MI-HIIT组	7	237.3±3.7	331.2±13.8	1.48±0.49	1.48±0.05^ab
MI-MICT组	7	234.5±4.1	345.0±43.0	1.32±0.50	1.16±0.11^c
F值		0.424	1.553	2.402	4.920
P值		0.738	0.232	0.098	0.010

表2 四组大鼠训练8周后BW、HW与标准化HMI比较（\d ±s）

Table 2 Comparison of body weight，heart weight and standardized cardiac mass index of four groups of rats at the end of 8 weeks of intervention

组别	只数	初始BW（g）	最终BW（g）	HW（g）	标准化HMI
Sham组	7	236.0±4.9	441.7±16.3	1.30±0.08	0.82±0.15
MI-SED组	7	235.0±4.8	426.7±27.9	1.14±0.15	1.15±0.15^a
MI-HIIT组	7	234.0±3.2	384.2±35.1^ab	1.52±0.06^ab	1.20±0.13^a
MI-MICT组	7	234.7±2.9	391.3±27.5^ab	1.33±0.04^bc	1.12±0.06^ac
F值		0.264	6.058	16.808	13.803
P值		0.850	0.004	<0.001	<0.001

表3 四组大鼠第4周心脏超声结果比较（\d ±s）

Table 3 Comparison of cardiac ultrasound results in four groups of rats at the end of 4 weeks of intervention

组别	只数	EF（%）	FS（%）	LVDs（mm）	LVDd（mm）	LVPWs（mm）	LVAWs（mm）
Sham组	7	74.62±2.11	46.10±2.51	3.02±0.62	5.57±1.02	2.10±0.45	3.05±0.36
MI-SED组	7	42.64±6.02^a	17.05±1.09^a	6.90±2.25^a	8.32±2.70^a	2.17±1.47	1.07±0.43^a
MI-HIIT组	7	69.77±7.53^ab	31.71±2.67^ab	5.02±0.21^ab	7.35±0.27^a	2.59±0.09	2.54±0.23^ab
MI-MICT组	7	65.88±2.82^ab	30.83±2.84^ab	4.47±0.27^ab	6.46±0.23^b	1.93±0.03	2.14±0.17^ab
F值		159.750	148.918	11.187	3.970	0.785	42.698
P值		<0.001	<0.001	<0.001	<0.001	0.516	<0.001

表4 四组大鼠第8周心脏超声结果比较（\d ±s）

Table 4 Comparison of cardiac ultrasound results in four groups of rats at the end of 8 weeks of intervention

组别	只数	EF（%）	FS（%）	LVDs（mm）	LVDd（mm）	LVPWs（mm）	LVAWs（mm）
Sham组	7	76.13±4.35	50.27±1.69	2.74±0.12	5.52±0.10	2.60±1.10	2.36±0.12
MI-SED组	7	28.73±8.02^a	19.34±7.03^a	2.65±0.27	3.29±0.25^a	1.30±0.16^a	2.35±0.58
MI-HIIT组	7	79.13±5.20^ab	35.00±2.12^ab	4.71±1.19^ab	7.24±0.18^ab	2.92±0.29^b	2.96±0.34^ab
MI-MICT组	7	72.11±2.89^ab	34.13±3.31^ab	4.34±1.08^ab	6.58±1.58^b	2.17±0.27^bc	2.24±0.74^c
F值		32.873	56.913	21.079	27.511	60.218	20.680
P值		<0.001	<0.001	<0.001	<0.001	<0.001	<0.001

图1 训练4周后大鼠心脏组织HE染色结果

Figure 1 H&E staining results of heart tissues in four groups of rats after 4 weeks of training

图2 训练8周后大鼠心脏组织HE染色结果

Figure 2 H&E staining results of heart tissues in four groups of rats after 8 weeks of training

图3 训练4周后大鼠心脏组织Masson染色

Figure 3 Masson's Trichrome staining results of heart tissues in four groups of rats after 4 weeks of training

图4 训练8周后大鼠心脏组织Masson染色

Figure 4 Masson's Trichrome staining results of heart tissues in four groups of rats after 8 weeks of training

表5 训练4周后各组心肌胶原纤维占比（Masson染色）、血管新生数（免疫组化CD31）及TNF-α比较（\d ±s）

Table 5 Comparison of the proportion of myocardial fibrillar collagen（Masson's Trichrome staining），angiogenesis （CD31immunohistochemistry staining）and serum TNF-α in four groups of rats at the end of 4 weeks of intervention

组别	只数	胶原纤维占比（%）	血管新生数（个/mm²）	TNF-α （pg/ml）
Sham组	7	0.7±0.3	229.2±52.1	8.2±2.0
MI-SED组	7	3.5±1.1^a	569.4±136.3^a	20.4±5.6^a
MI-HIIT组	7	2.3±0.9^a	1 035.0±152.3^ab	31.0±7.9^ab
MI-MICT组	7	2.6±0.7^a	883.0±398.8^ab	25.7±8.1^a
F值		12.539	15.039	14.118
P值		<0.001	<0.001	<0.001

表6 训练8周后各组心肌胶原纤维占比（Masson染色）、血管新生数（免疫组化CD31）及TNF-α比较（\d ±s）

Table 6 Comparison of the proportion of myocardial fibrillar collagen（Masson's Trichrome staining），angiogenesis （CD31 immunohistochemistry staining）and serum TNF-α in four groups of rats at the end of 8 weeks of intervention

组别	只数	胶原纤维占比（%）	血管新生数（个/mm²）	TNF-α （pg/ml）
Sham组	7	1.0±2.0	275.0±50.1	6.2±1.9
MI-SED组	7	6.6±2.9^a	513.9±155.0^a	14.3±2.9^a
MI-HIIT组	7	1.6±0.5^b	1 252.1±236.9^ab	18.8±3.8^a
MI-MICT组	7	2.4±1.1^b	1 022.9±134.4^abc	9.7±2.1^c
F值		15.817	48.189	23.506
P值		<0.001	<0.001	<0.001

图5 训练4周后大鼠心脏组织免疫组化结果（×200）

Figure 5 Immunohistochemical results of heart tissues in four groups of rats after 4 weeks of training

图6 训练8周后大鼠心脏组织免疫组化结果（×200）

Figure 6 Immunohistochemical results of heart tissues in four groups of rats after 8 weeks of training

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高强度间歇训练对心肌梗死大鼠心脏结构和功能的影响

Effects of High-intensity Interval Training on Cardiac Structure and Function in a Rat Model of Myocardial Infarction

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