| 吴超伦,丁巍,凌莉璐,丁峰.不同运动方式对慢性肾脏病小鼠心功能的影响及其机制研究[J].中国康复,2025,40(1):3-10 |
| 不同运动方式对慢性肾脏病小鼠心功能的影响及其机制研究 |
| Effects of different exercise methods on cardiac function in CKD mice and underlying mechanism |
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| DOI：10.3870/zgkf.2025.01.001 |
| 中文关键词: 高强度间歇运动 中等强度持续运动 慢性肾脏病 心脏功能 线粒体功能障碍 |
| 英文关键词: high intensity intermittent exercise moderate intensity continuous exercise chronic kidney disease heart function mitochondrial dysfunction |
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| 中文摘要: |
| 目的：探讨中等强度持续运动（MICT）和高强度间歇运动（HIIT）对慢性肾脏病（CKD）小鼠心脏功能的影响及其机制。方法：取24只6～8周龄雄性C57BL/6J小鼠随机分为假手术对照组（Sham组）、慢性肾衰静息组（CKD组）、慢性肾衰MICT组（CKD+MICT组）和慢性肾衰HIIT组（CKD+HIIT组）各6只。Sham组小鼠仅剥除肾膜，其余3组切除5/6肾脏建立慢性肾衰模型。CKD+MICT组和CKD+HIIT组小鼠术后进行2周适应性训练，后进行8周运动干预。干预结束后采用超声观察小鼠心脏形态和功能；检测血尿素氮（BUN）和血肌酐（SCr）评估肾脏功能；观察肾脏、心脏组织切片中病理损伤和纤维化情况；应用电镜观察心肌线粒体结构；通过Real-time PCR法测定心肌线粒体相关因子的表达：线粒体DNA（mtDNA）、NADH脱氢酶亚基1（ND-1）、过氧化物酶体增殖活化受体γ辅激活因子1α（PGC-1α）、线粒体转录因子A（TFAM）和三磷酸腺苷（ATP）合成酶；使用试剂盒检测心肌超氧化物歧化酶（SOD）活性与丙二醛（MDA）含量变化。结果：相较Sham组，其余3组体重、左室射血分数（LVEF）、舒张早期左室血流峰速/舒张晚期左室血流峰速（E/A值）、心肌总SOD活性、心肌mtDNA拷贝数、各项心肌线粒体相关因子的mRNA表达量明显下降（P<0.001，0.01，0.05）；SCr和BUN、肾小球损伤评分、肾小管纤维化指数、心肌纤维化指数、舒张早期左室血流峰速/舒张早期二尖瓣环血流速度（E/E’）值、心肌MDA含量明显升高（P<0.001，0.01，0.05）。相较CKD组，2组运动干预组体重、LVEF、E/A值、心肌总SOD活性、心肌mtDNA拷贝数、各项心肌线粒体指标表达量均升高（P<0.001，0.01，0.05）；血SCr和BUN、肾小球损伤评分、肾脏和心肌纤维化指数、E/E’值、心肌MDA含量、心肌线粒体肿胀空泡样程度均下降（P<0.001，0.01，0.05）。相较CKD+MICT组，CKD+HIIT组心肌MDA含量、E/E’值下降（P<0.001，0.01，0.05）；LVEF、E/A值、心肌总SOD活性、心肌mtDNA拷贝数、各项心肌线粒体指标表达量升高（P<0.01，0.05）。结论：HIIT和MICT均改善CKD小鼠心脏功能，HIIT改善效果更明显，这可能与减轻线粒体功能障碍、减少氧化应激损伤有关。 |
| 英文摘要: |
| Objective: To investigate the effects and mechanisms of moderate intensity continuous exercise (MICT) and high intensity intermittent exercise (HIIT) on cardiac function in mice with chronic kidney disease (CKD). Methods: A total of 24 male C57BL/6J mice aged 6-8 weeks were randomly divided into Sham group (n=6), CKD group (n=6), CKD+MICT group (n=6) and CKD+HIIT group (n=6). Only the renal capsule was removed in Sham group, and 5/6 kidneys were removed in other groups to establish CKD model. Mice in CKD+MICT group and CKD+HIIT group underwent 2 weeks adaptive training and exercise intervention for 8 weeks after surgery. After intervention, the heart morphology and function of mice were observed by ultrasound. Renal function was assessed by blood urea nitrogen (BUN) and serum creatinine (SCr). The pathological injury and fibrosis of kidney and heart tissue were observed. The structure of myocardial mitochondria was observed by electron microscopy. Mito-chondrial DNA（mtDNA）,NADH dehydrogenase subunit 1（ND-1）,peroxisome proliferator-activated receptor γ coactivator 1α（PGC-1α）,mitochondrial transcription factor A（TFAM） and ATP synthase were de-termined by real-time PCR. Finally, the changes of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in myocardium were detected with kit. Results: Compared with Sham group, body weight, left ventricular ejection fraction (LVEF), the ratio of early to late diastolic peak velocities (E/A value) , myocardial total SOD activity, myocardial mtDNA copy number and mRNA expression levels of myocardial mitochondria-related factors in the other 3 groups were significantly decreased (P<0.001,0.01，0.05). SCr and BUN, glomerular injury score, renal tubule fibrosis index, myocardial fibrosis index, the ratio of E-wave velocity to averaged E’ velocities of the mitral media and lateral annuli (E/E’value) and myocardial MDA content were significantly increased (P<0.001,0.01,0.05). Compared with CKD group, body weight, LVEF，E/A value, myocardial total SOD activity, myocardial mtDNA copy number and expression levels of myocardial mitochondrial indexes in 2 exercise intervention groups were increased (P<0.001,0.01,0.05). SCr and BUN, glomerular injury score, renal and myocardial fibrosis index, E/E’value，myocardial MDA content, and the degree of myocardial mitochondrial swelling and vacuolation were all decreased (P<0.001,0.01,0.05). Compared with CKD+MICT group，myocardial MDA content and E/E’value were decreased (P<0.001，0.01,0.05). LVEF，E/A value, myocardial total SOD activity, myocardial mtDNA copy number and expression levels of myocardial mitochondrial indexes of CKD+HIIT group were significantly increased (P<0.01,0.05).Conclusion: Both HIIT and MICT can improve the cardiac function of CKD mice, and HIIT can improve the cardiac function more significantly, which may be related to the reduction of mitochondrial dysfunction and oxidative stress damage. |
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