益生菌延緩骨骼肌減少的作用 –以高脂飲食給予高血壓大鼠為例

骨骼肌減少與老化、慢性疾病以及代謝異常引起的發炎或氧化壓力相關。近年研究發現腸道菌會調節發炎反應及氧化壓力，可能因此改善骨骼肌減少的狀態。益生菌 (probiotics)能幫助維持良好腸道菌相 (gut microbiota)，本研究旨在探討益生菌對高脂飲食誘導之高血壓大鼠所引起的骨骼肌減少之影響。本研究採用自發性高血壓大鼠 (spontaneously hypertensive rats, SHR)以高脂飲食 (high fat diet, HFD)誘導，模擬臨床上常見的代謝異常，測定肌肉組織。以正常組 (Wistar Kyoto rat, WKY組)、高脂高血壓對照組 (SHR組)以及高脂高血壓合併11種不同益生菌處理組 (編號SB1-11組)(N=6)。經12週處理後，與WKY組相比，SHR可顯著增加總膽固醇和血壓。高脂餵食高血壓鼠後，在各組間比目魚肌 (Soleus)與腓腸肌 (Gastrocnemius, GA)相對體重量並無顯著差異；且腓腸肌的組織切片在各組間亦無差異。在以慢縮氧化型肌纖維 (Type I)為主的比目魚肌組織中，與WKY組相比，高脂飲食的SHR組的的萎縮區域 (atrophy rate)增加，可能因此引起肌肉減少；與SHR組相比，每組益生菌組之比目魚肌atrophy rate皆有所降低，其中SB3、SB5與SB8組的比目魚肌atrophy rate分別減少為3.46%、5.01%與4.53% (p <0.01)；SB4與SB7組亦達統計顯著水準 (p <0.05)。肌肉組織中myogenic differentiation 1 (MyoD)與Myogenin (MyoG)結果顯示，腓腸肌在各組間無差異。而比目魚肌在高脂飲食組SHR較正常飲食組WKY之MyoG表現量顯著下降 (p <0.05)，顯示細胞分化能力受阻；與SHR組比較益生菌SB3組的MyoD與MyoG亦明顯增加 (p <0.001)，再生相關蛋白的表現顯著回升。在試管中檢測11種益生菌抗氧化力，以維生素C作為陽性對照組，SB1~SB11組確有抗氧化和金屬還原能力。綜合結果，益生菌可顯著減少高脂餵食高血壓鼠引起的比目魚肌萎縮程度，是否與益生菌抗氧化活性相關則須進一步探討。

Skeletal muscle atrophy is closely associated with aging, chronic diseases, and inflammation or oxidative stress resulting from metabolic abnormalities. Recent evidence suggests that gut microbiota can modulate inflammatory responses and oxidative stress, potentially ameliorating muscle loss. Probiotics are known to support a healthy gut microbiota. This study investigated the effects of probiotics on skeletal muscle atrophy induced by a high-fat diet (HFD) in spontaneously hypertensive rats (SHRs). SHRs were fed an HFD to model clinically relevant metabolic abnormalities. Experimental groups included a normal control group (Wistar Kyoto rats, WKY), an HFD-fed hypertensive control group (SHR), and eleven HFD-fed hypertensive groups treated with distinct probiotic strains (SB1–SB11; n = 6 per group). After 12 weeks of intervention, serum biochemical parameters, blood pressure, muscle mass, histological features, and myogenic regulatory factor expression were assessed. In vitro antioxidant activity of the probiotic strains was also evaluated using vitamin C as a positive control. Relative to WKY controls, SHRs exhibited significantly elevated total cholesterol levels and blood pressure (p < 0.05). No significant differences in relative soleus or gastrocnemius (GA) muscle weights were observed among groups, and GA histology showed no detectable differences. However, in the soleus muscle, which predominantly comprises slow-twitch oxidative (Type I) fibers, the atrophy rate was significantly higher in the HFD-fed SHR group than in the WKY group, indicating diet-induced muscle loss. Probiotic supplementation reduced the atrophy rate in all treated groups, with SB3, SB5, and SB8 demonstrating reductions of 3.46%, 5.01%, and 4.53%, respectively (p < 0.01), and SB4 and SB7 also showing significant reductions (p < 0.05). Expression analysis revealed no significant group differences in MyoD or myogenin (MyoG) levels in GA muscle. In soleus muscle, MyoG expression was significantly lower in HFD-fed SHRs compared with WKY rats (p < 0.05), suggesting impaired myogenic differentiation. Notably, the SB3 group exhibited significantly increased MyoD and MyoG expression compared with the SHR group (p < 0.001), indicating enhanced regenerative potential. Antioxidant assays confirmed that all probiotic strains exhibited both antioxidant and metal-reducing activities. Collectively, probiotic supplementation significantly attenuated soleus muscle atrophy in HFD-fed SHRs. The observed effects may be associated with the antioxidant properties of probiotics; however, further mechanistic studies are warranted to confirm this relationship.