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糖尿病肾病患者的血浆锌水平:与NLRP3炎性小体激活及肾脏预后是否存在关联?

Plasma Zinc Levels in Patients with Diabetic Nephropathy: Is there a Relationship with NLRP3 Inflammasome Activation and Renal Prognosis?

作者信息

Zhu Yuexin, Kang Dedong, Bai Xiaoying, Luo Ping, Du Bing, Li Bing

机构信息

Department of Nephrology, The Second Hospital of Jilin University, Changchun, 130041, Jilin, China.

Department of Anatomy, Showa University School of Medicine, Shinagawa-Ku, Tokyo, 142-8555, Japan.

出版信息

Biol Trace Elem Res. 2024 Sep 12. doi: 10.1007/s12011-024-04369-0.

Abstract

Zinc is an essential trace element, and impaired zinc homeostasis may be associated with inflammation in patients with diabetic nephropathy (DN). We investigated the influence of zinc level on nod-like receptor nucleotide-binding domain and leucine-rich repeat pyrin-3 domain (NLRP3) inflammasome expression and renal prognosis in patients with DN. We recruited 90 patients definitively diagnosed with DN by renal biopsy and 40 healthy controls. Zinc, NLRP3, interleukin (IL)-1β, and IL-18 levels were detected in blood samples, and the correlations between these parameters were assessed. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) evaluated the predictive value of zinc and the NLRP3 inflammasome for DN. Furthermore, patients with DN were divided into low- and normal-zinc groups to observe differences in clinical indicators and identify expression of inflammatory-related factors in renal tissue. Kaplan-Meier survival curves predicted the impact of zinc levels on renal prognosis. We found that the plasma zinc concentration in patients with DN was lower, while NLRP3, IL-1β, and IL-18 levels were higher than were those in patients without DN (P < 0.05). Zinc level was negatively correlated with NLRP3, IL-1β, and IL-18 levels (P < 0.01). Zinc and the NLRP3 inflammasome were predictive of DN, but their combination improved the diagnostic value. The DCA curve demonstrated a good positive net benefit in the combined model. Compared to patients with low zinc levels, patients with normal zinc levels had lower expression of NLRP3 inflammasome and a better prognosis. Zinc has a protective effect on DN and may affect NLRP3 inflammasome activation.

摘要

锌是一种必需的微量元素,糖尿病肾病(DN)患者体内锌稳态受损可能与炎症相关。我们研究了锌水平对DN患者中NOD样受体核苷酸结合结构域和富含亮氨酸重复序列的吡啉3结构域(NLRP3)炎性小体表达及肾脏预后的影响。我们招募了90例经肾活检确诊为DN的患者和40例健康对照者。检测血样中的锌、NLRP3、白细胞介素(IL)-1β和IL-18水平,并评估这些参数之间的相关性。采用受试者工作特征(ROC)曲线和决策曲线分析(DCA)评估锌和NLRP3炎性小体对DN的预测价值。此外,将DN患者分为低锌组和正常锌组,观察临床指标差异并确定肾组织中炎症相关因子的表达。Kaplan-Meier生存曲线预测锌水平对肾脏预后的影响。我们发现,DN患者的血浆锌浓度较低,而NLRP3、IL-1β和IL-18水平高于非DN患者(P<0.05)。锌水平与NLRP3、IL-1β和IL-18水平呈负相关(P<0.01)。锌和NLRP3炎性小体可预测DN,但二者联合可提高诊断价值。DCA曲线显示联合模型具有良好的正净效益。与低锌水平患者相比,正常锌水平患者的NLRP3炎性小体表达较低,预后较好。锌对DN具有保护作用,可能影响NLRP3炎性小体的激活。

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