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運動誘發鳶尾素對肥胖合併間歇性低氧引起心肌纖維化的影響

Effects of Exercise-Induced Irisin on Cardiac Fibrosis Resulted from the Combination of Obesity and Intermittent Hypoxia in Rats

摘要


本研究目的以動物模式模擬阻塞型睡眠呼吸中止症夜間之間歇性低氧現象,配合高脂飲食誘發肥胖,探討運動誘發鳶尾素對肥胖合併阻塞型睡眠呼吸中止症引起心肌纖維化的影響。將8週齡Sprague-Dawley雄性大鼠隨機先分成控制(control, CON)、間歇性低氧(intermittent hypoxia, IH)、運動(exercise, EXE)及IH配合EXE(IHEXE)組,各組再次分為正常飲食(normal diet, ND)及高脂飲食(high fat diet, HFD)2組,共計8組。運動訓練方式:在動物跑步機上進行12週運動訓練。IH模式:於第11 ~ 12週時,進行14天IH(8小時/天)曝露。動物犧牲後主要分析副睪及腎周邊脂肪量、比目魚肌及腓腸肌重量、心肌纖維化指標、腫瘤壞死因子-α(tumor necrosis factor-α, TNF-α)、介白素-6 (interleukin-6, IL-6)及骨骼肌鳶尾素表現量。研究結果顯示:與ND組比較,HFD導致CON、IH、EXE及IHEXE組之副睪及腎周邊脂肪量均明顯增加。與CON+ND組比較,CON+HFD及IH+ND組心肌纖維化指標、TNF-α 及IL-6表現量均明顯上升。在餵食ND及HFD各組間與IH組比較,EXE及IHEXE組均有較低副睪脂肪及腎周邊脂肪重量、心肌纖維化指標、心肌TNF-α及IL-6表現量與較高比目魚肌與體重比值、腓腸肌與體重比值及骨骼肌鳶尾素表現量。本研究結論為12週運動訓練增加骨骼肌鳶尾素表現量,可能與降低高脂飲食及間歇性低氧引起心肌纖維化的抗纖維化機轉有關。

並列摘要


The purpose of this study was to investigate whether irisin plays a key role in exercise-mediated effects on cardiac fibrosis in obese rats with obstructive sleep apnea (OSA). We used high-fat diet to develop obese animal model, which displays the intermittent hypoxia seen in OSA. Eight-week old male Sprague-Dawley rats were randomly assigned into control (CON), intermittent hypoxia (IH), exercise (EXE) and IH-induced in EXE (IHEXE) groups. Each group again divided into two subgroups, namely normal diet (ND) and high-fat diet (HFD) groups. The exercise and hypoxia protocols were explained as follows; exercise protocol: rats were trained on an animal treadmill for 12 weeks. IH exposure: at the week 11 and 12, rats were exposed to IH (8 hours/day) for 14 days. After the last treatment, rats were sacrificed, and the weights of epididymal fat, perirenal fat, soleus and gastrocnemius muscle were recorded. The myocardial levels of fibrosis index, concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and irisin expression in skeletal muscle were determined. The findings in this study showed that compared to ND, HFD feeding increased the weight of epididymal and perirenal fat in CON, IH, EXE and IHEXE groups. Compared to CON+ND group, rats in CON+HFD and IH+ND group showed significantly higher levels of cardiac fibrosis index, myocardial TNF-α and IL-6 concentrations (p < .05). We found lower weights of epididymal and perirenal fat, lower levels of cardiac fibrosis index, myocardial TNF-α and IL-6 in EXE and IHEXE rats compared to IH rats with ND and HFD. Moreover, higher soleus muscle to body weight ratio, gastrocnemius muscle to body weight ratio and upregulated irisin expression in skeletal muscle were found in EXE and IHEXE groups compared to IH group. In conclusion, 12-week exercise training can provide potent anti-fibrotic effects by attenuating the HFD- and IH-induced cardiac fibrosis in rats that is possibly through enhanced irisin expression in skeletal muscle.

並列關鍵字

sleep apnea high fat diet skeletal muscle

參考文獻


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