Dihydromyricetin Nanoparticles Alleviate Lipopolysaccharide-Induced Acute Kidney Injury by Decreasing Inflammation and Cell Apoptosis via the TLR4/NF-κB Pathway.

IF 5 3区 医学 Q1 ENGINEERING, BIOMEDICAL Journal of Functional Biomaterials Pub Date : 2024-08-29 DOI:10.3390/jfb15090249
Hongmei Yin, Qiaohua Yan, Yinglun Li, Huaqiao Tang
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Abstract

Acute kidney injury (AKI) is the most severe and fatal complication of sepsis resulting from infectious trauma. Currently, effective treatment options are still lacking. Dihydromyricetin is the main component extracted from Vine tea (Ampelopsis megalophylla Diels et Gilg). In our previous research, chitosan-tripolyphosphate-encapsulated nanoparticles of dihydromyricetin (CS-DMY-NPs) have been proven to have potential protective effects against cisplatin-induced AKI. Here, we investigated the protective effects and mechanisms of DMY and its nano-formulations against LPS-induced AKI by assessing pathological and inflammatory changes in mice. In mice with LPS-AKI treated with 300 mg/kg CS-DMY-NPs, the levels of creatinine (Cr), blood urea nitrogen (BUN), and KIM-1 were significantly reduced by 56%, 49%, and 88%, respectively. CS-DMY-NPs can upregulate the levels of GSH, SOD, and CAT by 47%, 7%, and 14%, respectively, to inhibit LPS-induced oxidative stress. Moreover, CS-DMY-NPs decreased the levels of IL-6, IL-1β, and MCP-1 by 31%, 49%, and 35%, respectively, to alleviate the inflammatory response. TUNEL and immunohistochemistry showed that CS-DMY-NPs reduced the number of apoptotic cells, increased the Bcl-2/Bax ratio by 30%, and attenuated renal cell apoptosis. Western blot analysis of renal tissue indicated that CS-DMY-NPs inhibited TLR4 expression and downregulated the phosphorylation of NF-κB p65 and IκBα. In summary, DMY prevented LPS-induced AKI by increasing antioxidant capacity, reducing inflammatory responses, and blocking apoptosis, and DMY nanoparticles were shown to have a better protective effect for future applications.

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二氢杨梅素纳米粒子通过TLR4/NF-κB途径减少炎症和细胞凋亡,从而缓解脂多糖诱发的急性肾损伤
急性肾损伤(AKI)是感染性创伤导致的败血症最严重、最致命的并发症。目前,仍缺乏有效的治疗方案。二氢杨梅素是从藤茶(Ampelopsis megalophylla Diels et Gilg)中提取的主要成分。在我们之前的研究中,壳聚糖-三聚磷酸钠包裹的二氢杨梅素纳米颗粒(CS-DMY-NPs)已被证实对顺铂诱导的 AKI 具有潜在的保护作用。在这里,我们通过评估小鼠的病理和炎症变化,研究了 DMY 及其纳米制剂对 LPS 诱导的 AKI 的保护作用和机制。用 300 毫克/千克 CS-DMY-NPs 治疗 LPS-AKI 小鼠,肌酐(Cr)、血尿素氮(BUN)和 KIM-1 的水平分别显著降低了 56%、49% 和 88%。CS-DMY-NPs 能使 GSH、SOD 和 CAT 的水平分别提高 47%、7% 和 14%,从而抑制 LPS 诱导的氧化应激。此外,CS-DMY-NPs 还能使 IL-6、IL-1β 和 MCP-1 的水平分别降低 31%、49% 和 35%,从而缓解炎症反应。TUNEL 和免疫组化显示,CS-DMY-NPs 减少了凋亡细胞的数量,使 Bcl-2/Bax 比率增加了 30%,并减轻了肾细胞的凋亡。肾组织的 Western 印迹分析表明,CS-DMY-NPs 可抑制 TLR4 的表达,并下调 NF-κB p65 和 IκBα 的磷酸化。总之,DMY通过增加抗氧化能力、减少炎症反应和阻断细胞凋亡来预防LPS诱导的AKI,DMY纳米颗粒具有更好的保护效果,可用于未来的应用。
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来源期刊
Journal of Functional Biomaterials
Journal of Functional Biomaterials Engineering-Biomedical Engineering
CiteScore
4.60
自引率
4.20%
发文量
226
审稿时长
11 weeks
期刊介绍: Journal of Functional Biomaterials (JFB, ISSN 2079-4983) is an international and interdisciplinary scientific journal that publishes regular research papers (articles), reviews and short communications about applications of materials for biomedical use. JFB covers subjects from chemistry, pharmacy, biology, physics over to engineering. The journal focuses on the preparation, performance and use of functional biomaterials in biomedical devices and their behaviour in physiological environments. Our aim is to encourage scientists to publish their results in as much detail as possible. Therefore, there is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Several topical special issues will be published. Scope: adhesion, adsorption, biocompatibility, biohybrid materials, bio-inert materials, biomaterials, biomedical devices, biomimetic materials, bone repair, cardiovascular devices, ceramics, composite materials, dental implants, dental materials, drug delivery systems, functional biopolymers, glasses, hyper branched polymers, molecularly imprinted polymers (MIPs), nanomedicine, nanoparticles, nanotechnology, natural materials, self-assembly smart materials, stimuli responsive materials, surface modification, tissue devices, tissue engineering, tissue-derived materials, urological devices.
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