Zinc (Zn), as an essential trace element, has been approved to serve many roles in diabetic studies. Also Zn deficiency will aggravate renal damage in diabetes through suppression of nuclear factor-erythroid 2-related factor 2 (Nrf2) expression and function. The purpose of this study was to illustrate the role of Zn in renal apoptosis in diabetes and whether Nrf2 participated in the process. Type 2 diabetes mice model was induced by a single dose of streptozotocin (STZ) injection after high-fat diet (HFD) feeding for 3 months, then the mice were given diets supplemented with different concentrations of Zn (control, 30 ppm; low-concentration, 0.85 ppm). After 12-week treatment, morphology and associated protein expressions were examined. The results showed that low Zn diet significantly aggravated the level of renal apoptosis during diabetes, performed as the upregulation of caspase-3 expression. In addition, either low Zn diet or diabetes or both dramatically decreased the expression of Nrf2 and P-AKT in kidney. Moreover, the expression of β-catenin in kidney was increased markedly in diabetic groups. Mechanistic study applying human renal tubular epithelial cells (HK11) confirmed the role of Nrf2, as silencing Nrf2 expression abolished Zn supplementation protection against high sugar + high fat + low Zn-induced apoptosis and downregulation of β-catenin expression. All these results suggest that Nrf2 plays a key role in Zn protection against Type 2 diabetes induced renal apoptosis, which might be through Wnt/β-catenin signaling pathway.

锌（Zn）作为必需的微量元素，已被批准在糖尿病研究中发挥许多作用。锌缺乏也会通过抑制核因子-类红细胞2相关因子2（Nrf2）的表达和功能来加重糖尿病对肾脏的损害。这项研究的目的是为了说明锌在糖尿病肾细胞凋亡中的作用以及Nrf2是否参与了该过程。在高脂饮食（HFD）喂养3个月后，通过单剂量链脲佐菌素（STZ）注射诱导了2型糖尿病小鼠模型，然后给小鼠饮食添加了不同浓度的锌（对照组为30 ppm；低剂量浓度为0.85 ppm）。治疗12周后，检查形态和相关蛋白表达。结果表明，低锌饮食会显着加重糖尿病患者的肾脏细胞凋亡水平，表现为caspase-3表达的上调。此外，低锌饮食或糖尿病或两者都显着降低肾脏中Nrf2和P-AKT的表达。此外，糖尿病组肾脏中β-catenin的表达明显增加。应用人肾小管上皮细胞（HK11）的机理研究证实了Nrf2的作用，因为沉默Nrf2表达取消了锌补充保护，防止高糖+高脂肪+低锌诱导的细胞凋亡和β-catenin表达下调。所有这些结果表明，Nrf2在锌对2型糖尿病诱导的肾细胞凋亡的保护中起着关键作用，这可能是通过Wnt /β-catenin信号通路引起的。低锌饮食或糖尿病或两者都显着降低肾脏中Nrf2和P-AKT的表达。此外，糖尿病组肾脏中β-catenin的表达明显增加。应用人肾小管上皮细胞（HK11）的机理研究证实了Nrf2的作用，因为沉默Nrf2表达取消了锌补充保护，防止高糖+高脂肪+低锌诱导的细胞凋亡和β-catenin表达下调。所有这些结果表明，Nrf2在锌对2型糖尿病诱导的肾细胞凋亡的保护中起着关键作用，这可能是通过Wnt /β-catenin信号通路引起的。低锌饮食或糖尿病或两者都显着降低肾脏中Nrf2和P-AKT的表达。此外，糖尿病组肾脏中β-catenin的表达明显增加。应用人肾小管上皮细胞（HK11）的机理研究证实了Nrf2的作用，因为沉默Nrf2表达取消了锌补充保护，防止高糖+高脂肪+低锌诱导的细胞凋亡和β-catenin表达下调。所有这些结果表明，Nrf2在锌对2型糖尿病诱导的肾细胞凋亡的保护中起着关键作用，这可能是通过Wnt /β-catenin信号通路引起的。因为沉默Nrf2表达取消了Zn补充保护，防止高糖+高脂肪+低Zn诱导的细胞凋亡和β-catenin表达下调。所有这些结果表明，Nrf2在锌对2型糖尿病诱导的肾细胞凋亡的保护中起着关键作用，这可能是通过Wnt /β-catenin信号通路引起的。因为沉默Nrf2表达取消了Zn补充保护，防止高糖+高脂肪+低Zn诱导的细胞凋亡和β-catenin表达下调。所有这些结果表明，Nrf2在锌对2型糖尿病诱导的肾细胞凋亡的保护中起着关键作用，这可能是通过Wnt /β-catenin信号通路引起的。