Purpose

To investigate how sleeve gastrectomy (SG), a typical operation of bariatric surgery, attenuated symptom, and progression of diabetic kidney disease (DKD).

Methods

DKD model was induced by high-fat diet (HFD) combined with streptozocin in Wistar rats. SG was performed, and the group subjected to sham surgery served as control. The animals were euthanized 12 weeks after surgery, followed by sample collection for the subsequent experiment. The HK-2, a renal proximal tubular epithelial cell line derived from human, was utilized to investigate the potential mechanisms.

Results

SG improved metabolic parameters and glucose homeostasis, and could alleviate DKD in terms of renal function indices as well as histological and morphological structures in DM rats, accompanied with a significant reduction in renal tubular injury. Compared with sham group, SG reduced the renal tubular ferroptosis. To further clarify the mechanism involved, in vitro experiments were performed. In the presence of high glucose, renal tubular TGF-β1 secretion was significantly increased in HK-2 cell line, which led to activation of ferroptosis through TGF-β1/Smad3 signaling pathway. Inhibition of TGF-β1 receptor and phosphorylation of Smad3 significantly ameliorated TGF-β1-mediated ferroptosis. In vivo experiments also found that SG improved the hyperglycemic environment, reduced renal TGF-β1 concentrations, and down-regulated the TGF-β1/Smad3 signaling pathway.

Conclusions

With the capacity to lower the glucose, SG could attenuate the ferroptosis by inhibiting TGF-β1/Smad3 signaling pathway in DKD rats, and eventually attenuated DKD.

中文翻译：

---

袖状胃切除术通过下调 TGF-β1/Smad3 信号通路将糖尿病肾病的减轻与肾小管铁死亡的抑制联系起来

目的

探讨袖状胃切除术（SG）（一种典型的减肥手术）如何减轻糖尿病肾病（DKD）的症状和进展。

方法

采用高脂饮食（HFD）联合链脲佐菌素诱导Wistar大鼠DKD模型。进行SG，假手术组作为对照。手术后12周对动物实施安乐死，然后收集样本用于后续实验。 HK-2（一种源自人的肾近端肾小管上皮细胞系）被用来研究其潜在机制。

结果

SG可改善DM大鼠的代谢参数和葡萄糖稳态，并可减轻DM大​​鼠的肾功能指标以及组织学和形态结构方面的DKD，同时显着减少肾小管损伤。与假手术组相比，SG减少了肾小管铁死亡。为了进一步阐明所涉及的机制，进行了体外实验。在高糖存在下，HK-2细胞系中肾小管TGF-β1分泌显着增加，从而通过TGF-β1/Smad3信号通路导致铁死亡的激活。抑制 TGF-β1 受体和 Smad3 磷酸化可显着改善 TGF-β1 介导的铁死亡。体内实验还发现SG改善高血糖环境，降低肾脏TGF-β1浓度，下调TGF-β1/Smad3信号通路。

结论

SG具有降糖作用，可通过抑制DKD大鼠的TGF-β1/Smad3信号通路来减轻铁死亡，最终减轻DKD。