作为儿童罕见疾病，坏死性小肠结肠炎（NEC）导致高发病率和死亡率，但其病理生理学尚不明确。TRPM7是一种膜蛋白，在炎症反应中发挥关键作用。本研究旨在研究TRPM7对儿童NEC的促进作用，并探索TRPM7抑制剂NS8593的治疗作用。首先，我们通过定量实时聚合酶链反应（RT-PCR）、Western blot和酶联免疫吸附实验检测了儿童NEC患者的TRPM7和NLR家族脉络蛋白结构域含有3（NLRP3）表达及炎症状态。然后，我们用脂多糖（LPS）诱导人类肠上皮细胞系产生NEC，并通过RT-PCR和流式细胞术检测细胞因子和反应性氧气种类（ROS）水平。通过荧光检测确定了TRPM7介导的钙离子通量。此外，我们使用TRPM7抑制剂NS8593治疗活体大鼠模型，通过实时PCR和酶联免疫吸附分析测定了mRNA和蛋白质表达。与对照样本相比，儿童NEC的样本中TRPM7和NLRP3表达更高。此外，在患有NEC的儿童血清中还检测出白细胞介素-1β、白细胞介素-6和肿瘤坏死因子α等细胞因子的升高分泌。这些结果表明，TRPM7通过激活NLRP3在NEC发展中具有促进作用。为了验证我们的假设，我们使用TRPM7抑制剂NS8593治疗法脂多糖（LPS）刺激的IEC-6细胞。我们发现，TRPM7抑制剂NS8593抑制了LPS诱导的细胞因子产生，并通过缓解TRPM7介导的NLRP3炎性小体激活发挥了抗炎作用。通过活体实验，我们发现TRPM7参与了NEC的发生，并且其抑制剂NS8593在大鼠模型中具有一定的治疗作用。我们的研究表明，TRPM7抑制剂减轻了LPS诱导的ROS并减少了炎症性细胞因子的释放，对NEC模型具有保护作用。2022年儿科转化医学。保留所有权利。

As a rare disease in children, necrotizing enterocolitis (NEC) leads to high morbidity and mortality. However, its pathophysiology is largely unclear. Transient receptor potential melastatin 7 (TRPM7) is a membrane protein, which plays key roles in the inflammatory response. This study sought to examine the promoting effect of TRPM7 on NEC in children and explore the therapeutic effect of a TRPM7 inhibitor NS8593.First, we detected TRPM7 and NLR family pyrin domain containing 3 (NLRP3) expression and the state of inflammation in children with NEC through quantitative real-time polymerase chain reaction (RT-PCR), Western blot, and enzyme-linked immunosorbent assays. Next, Human intestinal epithelial cell lines were induced to NEC by lipopolysaccharides (LPSs). The level of cytokines and reactive oxygen species (ROS) were tested by RT-PCR and flow cytometry. The TRPM7 mediated calcium flux were determined by fluorescence. In addition, we used the TRPM7 inhibitor NS8593 to treat the in vivo rat model. The mRNA and protein expression were determined by real-time PCR and Elisa analysis, respectively.TRPM7 and NLRP3 expression was more increased in the samples from children with NEC compared to the control samples. Additionally, the elevated secretion of interleukin-1β, interleukin-6, and tumor necrosis factor alpha was also detected in the serum of children with NEC. These results showed that TRPM7 had a promoting effect on NEC development, possibly via the activation of NLRP3. To test our hypothesis, the TRPM7 inhibitor NS8593 was used to treat the LPS-stimulated IEC-6 cells. We found that the TRPM7 inhibitor NS8593 inhibited LPS-induced cytokine production and exhibited an anti-inflammatory effect by alleviating TRPM7-mediated NLRP3 inflammasome activation. Through in-vivo experiments, we found that TRPM7 was involved in the occurrence of NEC, and its inhibitor NS8593 played a certain therapeutic role in the rat model.Our study revealed TRPM7 inhibitors attenuated LPS-induced ROS and reduced the release of pro-inflammatory cytokines. It also exhibited protective effects on the NEC model.2022 Translational Pediatrics. All rights reserved.