本研究旨在合成乳清蛋白纳米颗粒（WPNPs），用于三种水平的柠檬酸锌（Zn CITR）包衣，并研究它们对四氯化碳（CCl4）诱导的大鼠肾脏损伤和炎症基因表达紊乱的保护作用。将70只雄性斯普拉格-道利大鼠分为七组，并经口处理4周，具体如下：对照组，两次每周给予CCl4（5 mL/kg体重），CCl4加WPNPs（300 mg/kg体重）组，给予50 mg/kg体重的Zn CITR组，以及低、中、高剂量（LD、MD和HD）的Zn CITR-WPNPs三个配方组。收集血液和肾脏样本进行不同的检测和组织学分析。制备的颗粒呈半球形，平均尺寸为160 ± 2.7、180 ± 3.1和200 ± 2.6 nm，ζ电位分别为-126、-93和-84 mV，适用于ZN CITR-WPNPs（LD）、Zn CITR-WPNPs（MD）和ZN CITR-WPNPs（HD）。CCl4显著增加了（p ≤ 0.05）肾功能指标、氧化应激标志物、转化生长因子-β1、白介素（IL）-1β、IL-10、IL-6、诱导型一氧化氮合酶和肿瘤坏死因子-α的信使RNA表达，并显著降低了（p ≤ 0.05）肾超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶以及肾组织的组织学变化。WPNPs、Zn CITR和载荷Zn CITR的WPNPS对这些并发症具有保护作用，其中Zn CITR-WPNPs（LD）效果更显著。WPNPs可以有效地用于包衣Zn CITR，并且以每克WPNPs 7 mg的水平作为肾脏保护的补充剂，以增强免疫力并避免过多锌的危害。©2023 Wiley Periodicals LLC.

This work was conducted to synthesize whey protein nanoparticles (WPNPs) for the coating of zinc citrate (Zn CITR) at three levels and to study their protective role against CCl4 -induced kidney damage and inflammatory gene expression disorder in rats. Seventy male Sprague-Dawley rats were divided into seven groups and treated orally for 4 weeks as follows; the control group, the group treated twice a week with CCl4 (5 mL/kg b.w), the groups received CCl4 plus WPNPs (300 mg/kg b.w); the group received 50 mg/kg b.w of Zn CITR or the three formulas of Zn CITR-WPNPs at low, medium and high doses (LD, MD, and HD). Blood and kidney samples were collected for different assays and histological analyses. The fabricated particles were semispherical, with an average size of 160 ± 2.7, 180 ± 3.1, and 200 ± 2.6 nm and ζ potential of -126, -93, and -84 mV for ZN CITR-WPNPs (LD), Zn CITR-WPNPs (MD), and ZN CITR-WPNPs (HD), respectively. CCl4 significantly increased (p ≤ 0.05) kidney function indices, oxidative stress markers, messenger RNA expression of transforming growth factor-β1, interleukin (IL)-1β, IL-10, IL-6, inducible nitric oxide synthase, and tumor necrosis factor-α and significantly decreased (p ≤ 0.05) renal superoxide dismutase, catalase, and glutathione peroxidase along with the histological changes in the kidney tissues. WPNPs, Zn CITR, and Zn CITR loaded WPNPS showed a protective effect against these complications and Zn CITR-WPNPs (LD) was more effective. WPNPs can be used effectively for coating Zn CITR at a level of 7 mg/g WPNPs to be used as a supplement for the protection of the kidney against different toxicants to enhance immunity and avoid harm of excess Zn.© 2023 Wiley Periodicals LLC.