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茶多酚通过改善肌肉脂肪浸润延缓衰老T2DM模型大鼠肌肉衰减机制

Mechanism of tea polyphenols delaying sarcopenia in the rat model of aged T2DM by ameliorating muscle fat infiltration

  • 摘要:
    目的 基于Wnt/β-catenin通路探讨茶多酚(Tea polyphenols, TP)通过改善肌肉脂肪浸润减缓衰老T2DM模型大鼠腓肠肌肌肉衰减的机制。
    方法 30只8 w龄SD大鼠,按体重分为对照组和造模组。利用高糖高脂饲养及注射STZ诱导T2DM,腹腔注射D–半乳糖诱导衰老,从而构建衰老T2DM大鼠模型。空腹血糖(FBG)≥16.7 mmol/L以及腓肠肌P53蛋白表达明显高于对照组分别作为糖尿病和衰老发生的判定标准。实验中对照组、衰老T2DM组及TP干预组(7w造模成功后,300 mg/kg TP连续干预8w)进行比较分析。大鼠腓肠肌相对湿重、HE染色观察并半定量分析肌间脂肪组织的面积,Western blot法检测腓肠肌Wnt10b、β-catenin、PPAR-γ、CEBPB等蛋白的表达。
    结果 与模型组相比,TP干预组大鼠FBG水平在干预结束时降低(P<0.05)、腓肠肌相对湿重平均提高约38.10%(P<0.05)、肌间脂肪浸润平均减少约18.60%(P<0.05)。此外,TP干预后胰腺组织结构在形状、面积及胰岛细胞的胞浆疏松或空泡化程度较模型组有较明显改善。腓肠肌Wnt10b和β-catenin蛋白表达水平上调,PPARγ和CEBPB蛋白表达水平下降(均P<0.05)。
    结论 TP干预可以改善肌肉质量,减少腓肠肌脂肪浸润,其部分作用机理可能与激活Wnt/β-catenin信号通路调控下游脂肪细胞的分化有关。

     

    Abstract:
    Objective To investigate the effect of tea polyphenols (TP) on sarcopenia in the rat model of type 2 diabetes mellitus (T2DM) by regulating the Wnt/β-catenin pathway.
    Methods Thirty 8-week-old SD rats were assigned into a control group (n=10) and a modeling group (n=20) according to body weight. The aged T2DM model was induced by a high-sugar and high-fat diet combined with injection of D-galactose and streptozotocin (STZ). Fasting blood glucose (FBG) ≥16.7 mmol/L and elevated P53 protein expression mark the occurrence of diabetes and aging. The relative wet weight of gastrocnemius muscle was compared among the control, model, and TP intervention (administration with TP at 300 mg/kg for 8 consecutive weeks after modeling for 7 weeks) groups. The area of intermuscular adipose tissue was observed via hematoxylin-eosin staining and semi-quantitatively analyzed. The expression levels of proteins including Wnt10b, β-catenin, PPAR-γ, and CEBPB in the gastrocnemius muscle were determined by Western blot.
    Results The TP intervention group had lower FBG, higher relative wet weight of gastrocnemius muscle, and lower intermuscular fat infiltration (a decrease of 18.60%) at the end of the intervention than the model group (all P<0.05). TP intervention improved the pancreatic tissue structure in shape and area and alleviated the vacuolation of islet cells compared with the model group. In addition, TP intervention up-regulated the expression of Wnt10b and β-catenin while down-regulating the expression of PPARγ and CEBPB (all P<0.05).
    Conclusions TP intervention may improve muscle mass and reduce fat infiltration in the gastrocnemius muscle by activating the Wnt/β-catenin signaling pathway that regulates the differentiation of adipocytes.

     

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