Background

Renal interstitial fibrosis is the pathophysiological basis of type 2 diabetes mellitus (T2DM). Exercise appears to improve kidney interstitial fibrosis in T2DM, in which silent information regulator factor 2-related enzyme 1 (Sirt1) is a critical regulator. However, the role of Sirt1 in mediating exercise on renal tissue as well as its mechanism remains unknown.

Methods

T2DM mouse models were created using a high-fat diet mixed with streptozotocin, followed by 8 weeks of treadmill exercise and niacinamide (Sirt1 inhibitor) intervention. Kits for detecting biochemical indices of renal function were used. The pathological appearance and severity of renal tissue were examined using hematoxylin and eosin, Masson and immunohistochemical staining. The mRNA and protein expression of relevant signaling pathway factors were determined to use real-time reverse transcriptase-polymerase chain reaction and western blotting.

Results

T2DM can promote renal interstitial fibrosis, increase kidney index, serum creatinine, blood urea nitrogen and 24 h urinary total protein and cause pathological changes in renal tissue and affect renal function. After 8 weeks of exercise intervention, the biochemical indicators in the kidney of T2DM mice were decreased, Sirt1 expression was increased, the expression of TGF-β1, Smad3, collagen type I (COL1) and collagen type III (COL3) were decreased, and the renal interstitial fibrosis, renal tissue structural lesions and renal function were improved. However, after the nicotinamide intervention, renal interstitial fibrosis of T2DM mice was aggravated, and the improvement effect of exercise on renal interstitial fibrosis of T2DM mice was abolished.

Conclusion

The upregulation of Sirt1 expression by exercise can inhibit the transforming growth factor β1/Smad3 pathway, thereby inhibiting the expression and deposition of COL1 and COL3 in renal interstitium, thereby improving renal interstitial fibrosis in T2DM.

中文翻译：

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运动通过改善 T2DM 小鼠 Sirt1 介导的 TGF-β1/Smad3 通路来减轻肾间质纤维化

背景

肾间质纤维化是2型糖尿病（T2DM）的病理生理基础。运动似乎可以改善 T2DM 的肾间质纤维化，其中沉默信息调节因子 2 相关酶 1 (Sirt1) 是一个关键的调节因子。然而，Sirt1在介导肾组织运动中的作用及其机制仍不清楚。

方法

T2DM 小鼠模型采用高脂饮食和链脲佐菌素混合，然后进行 8 周的跑步机运动和烟酰胺（Sirt1 抑制剂）干预。使用检测肾功能生化指标的试剂盒。使用苏木精和伊红、Masson 和免疫组织化学染色检查肾组织的病理外观和严重程度。采用实时逆转录聚合酶链反应和蛋白质印迹法测定相关信号通路因子的mRNA和蛋白表达。

结果

T2DM可促进肾间质纤维化，肾指数、血肌酐、血尿素氮、24h尿总蛋白升高，引起肾组织病理改变，影响肾功能。运动干预8周后,T2DM小鼠肾脏生化指标降低,Sirt1表达升高,TGF-β1、Smad3、I型胶原(COL1)和III型胶原(COL3)表达降低,肾间质纤维化、肾组织结构病变及肾功能得到改善。但烟酰胺干预后，T2DM小鼠肾间质纤维化加重，运动对T2DM小鼠肾间质纤维化的改善作用被取消。

结论

运动上调Sirt1表达可以抑制转化生长因子β1/Smad3通路，从而抑制COL1和COL3在肾间质的表达和沉积，从而改善T2DM肾间质纤维化。