潘万东,汤静,刘晓哲,等.有氧运动对非酒精性脂肪性肝病大鼠肝脏纤维化的影响及机制研究[J].中华物理医学与康复杂志,2024,46(8):687-691
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| 有氧运动对非酒精性脂肪性肝病大鼠肝脏纤维化的影响及机制研究 |
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| DOI：10.3760/cma.j.issn.0254-1424.2024.08.003 |
| 中文关键词: 有氧运动 非酒精性脂肪性肝病 肝脏纤维化 肝星状细胞 炎症 细胞外基质 |
| 英文关键词: Aerobic exercise Liver disease Liver fibrosis Hepatic stellate cells Inflammation Extracellular matrix |
| 基金项目:河南省重点科技攻关项目（242102321140） |
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| 中文摘要: |
| 目的 探讨规律有氧运动对非酒精性脂肪性肝病（NAFLD）大鼠肝纤维化的影响及作用机制，为优化NAFLD患者康复运动处方提供参考依据。 方法 采用随机数字表法将24只8周龄雄性OLETF大鼠分为模型安静组和模型运动组，每组12只大鼠，另选取12只鼠龄、性别与之匹配的同品系LETO大鼠纳入健康对照组。模型运动组大鼠给予12周跑台运动训练，健康对照组及模型安静组大鼠则同期保持安静状态。于12周跑台训练结束后采用比色法检测3组大鼠空腹血糖、胰岛素及糖化血红蛋白（HbA1c）含量，然后处死大鼠提取肝脏组织，通过肝脏Masson染色进行组织病理学观察并获取胶原容积分数，采用明胶酶谱法检测肝脏基质金属蛋白酶-2（MMP-2）和MMP-9活性，采用免疫印迹法检测肝脏白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、α平滑肌肌动蛋白（αSMA）、富半胱氨酸蛋白61（CCN1）、转化生长因子-β（TGF-β）、MMP-12及金属蛋白酶组织抑制物-1（TIMP-1）蛋白表达量。 结果 与健康对照组比较，模型安静组大鼠体重、空腹血糖、空腹胰岛素、HbA1c、肝脏胶原容积分数均显著升高（P<0.05），MMP-2及MMP-9活性则明显降低（P<0.05），TGF-β、αSMA、CCN1、IL-1β、TNF-α、MMP-12蛋白表达量均明显上调。与模型安静组比较，模型运动组大鼠空腹血糖、空腹胰岛素、HbA1c、肝脏胶原容积分数均显著降低（P<0.05），肝脏MMP-2、MMP-9活性及CCN1蛋白表达量均显著升高（P<0.05），TGF-β、αSMA、IL-1β、TNF-α、MMP-12蛋白表达量均显著下调（P<0.05），体重水平组间差异则无统计学意义（P>0.05）。 结论 规律有氧运动能延缓NAFLD大鼠肝脏纤维化，其作用机制可能与抑制肝脏炎性反应和肝星状细胞活化以及改善细胞外基质重塑有关。 |
| 英文摘要: |
| Objective To explore any effect of regular aerobic exercise on liver fibrosis in rats with non-alcoholic fatty liver disease (NAFLD) and its mechanism. Methods Twenty-four 8-week-old male OLETF rats were randomly divided into a model sedentary group and a model exercise group, each of 12. Twelve age- and sex-matched LETO rats of the same strain were selected into the healthy control group. The model exercise group underwent treadmill exercise training for 12 weeks, while the other two groups undertook no exercise. After the training, fasting blood glucose, insulin and glycosylated hemoglobin (HbA1c) were measured using colorimetry. Liver tissue was resected to observe any histopathological changes using Masson staining and to measure the collagen volume fraction. Zymography was applied to determine the activities of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the liver. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), α-smooth muscle actin (αSMA), cysteine-rich protein 61 (CCN1), transforming growth factor-β (TGF-β), MMP-12 and the tissue inhibitor of metalloproteinase-1 (TIMP-1) proteins in the liver were quantified using western blotting. Results Compared with the healthy control group, the model sedentary group on average displayed a significant increase in body weight, fasting blood glucose, fasting insulin, HbA1c, liver collagen volume fraction, and the protein expression of TGF-β, αSMA, CCN1, IL-1β, TNF-α, and MMP-12. There was a significant decrease in the activity of MMP-2 and MMP-9 on average. Compared with the model sedentary group, the model exercise group on average displayed lower fasting blood glucose, fasting insulin, HbA1c, and liver collagen volume fraction, as well as less expression of TGF-β, αSMA, IL-1β, TNF-α, and MMP-12 protein. MMP-2 and MMP-9 activity was higher, as was the expression of CCN1 protein. There were no significant differences in average body weight between the model sedentary and exercise groups. Conclusion Regular exercise can delay liver fibrosis, at least in NAFLD rats. The mechanism is related to inhibiting hepatic inflammatory response, the activation of hepatic stellate cells and improving extracellular matrix remodeling. |
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