BAPTA-AM 脂质体纳米颗粒消除细胞内 Ca2+ 超载:一种治疗急性胰腺炎的有效方法

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
International journal of molecular medicine Pub Date : 2024-04-01 Epub Date: 2024-02-23 DOI:10.3892/ijmm.2024.5358
Zailin Fu, Dingsheng Wang, Caiyun Zheng, Minghua Xie, Yifang Chen, Yi Zhou, Yan Huang, Ying Song, Weiyong Hong
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引用次数: 0

摘要

钙超载是急性胰腺炎(AP)的一个显著诱因,它会诱发氧化应激和炎症级联反应,继而激活内源性和外源性细胞凋亡途径。然而,目前缺乏通过解决钙超载来缓解急性胰腺炎的药物干预措施。本研究探讨了脂质体纳米颗粒(LNs)作为一种细胞渗透性钙螯合剂--1,2-双(2-氨基苯氧基)乙烷-N,N,N',N'-四乙酸四(乙酰氧甲基酯)(BAPTA-AM)--治疗 AP 的潜在临床应用。为了在体外建立实验模型,将 AR42J 细胞暴露于高糖/油酸钠(HGO)以诱导坏死,在体内则使用导管内注入牛磺胆酸盐(TC)来诱导 AP。本研究结果表明,使用负载BAPTA-AM的LN(BLN)能有效、快速地消除过量的Ca2+和活性氧,抑制单核巨噬细胞的活化和炎性细胞因子的释放,减轻HGO诱导的胰腺尖叶细胞凋亡和坏死。此外,在大鼠 AP 模型中,BLN 的全身给药显示出良好的治疗潜力。值得注意的是,BLN 能显著提高接受 TC 挑战的大鼠的存活率,从 37.5% 提高到 75%。血液生化指标的改善和胰腺病变的减轻表明,胰腺功能得到了恢复。BLN 在抢救 AP 患者方面的潜在疗效可能归功于其抑制氧化应激、防止酶原过早活化以及下调 TNF-α、IL-6 和 cathepsin B 表达的能力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Elimination of intracellular Ca2+ overload by BAPTA‑AM liposome nanoparticles: A promising treatment for acute pancreatitis.

Calcium overload, a notable instigator of acute pancreatitis (AP), induces oxidative stress and an inflammatory cascade, subsequently activating both endogenous and exogenous apoptotic pathways. However, there is currently lack of available pharmaceutical interventions to alleviate AP by addressing calcium overload. In the present study, the potential clinical application of liposome nanoparticles (LNs) loaded with 1,2‑bis(2‑aminophenoxy)ethane‑N,N,N',N'‑tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA‑AM), a cell‑permeant calcium chelator, was investigated as a therapeutic approach for the management of AP. To establish the experimental models in vitro, AR42J cells were exposed to high glucose/sodium oleate (HGO) to induce necrosis, and in vivo, intra‑ductal taurocholate (TC) infusion was used to induce AP. The findings of the present study indicated that the use of BAPTA‑AM‑loaded LN (BLN) effectively and rapidly eliminated excessive Ca2+ and reactive oxygen species, suppressed mononuclear macrophage activation and the release of inflammatory cytokines, and mitigated pancreatic acinar cell apoptosis and necrosis induced by HGO. Furthermore, the systemic administration of BLN demonstrated promising therapeutic potential in the rat model of AP. Notably, BLN significantly enhanced the survival rates of rats subjected to the TC challenge, increasing from 37.5 to 75%. This improvement was attributed to the restoration of pancreatic function, as indicated by improved blood biochemistry indices and alleviation of pancreatic lesions. The potential therapeutic efficacy of BLN in rescuing patients with AP is likely attributed to its capacity to inhibit oxidative stress, prevent premature activation of zymogens and downregulate the expression of TNF‑α, IL‑6 and cathepsin B. Thus, BLN demonstrated promising value as a novel therapeutic approach for promptly alleviating the burden of intracellular Ca2+ overload in patients with AP.

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来源期刊
International journal of molecular medicine
International journal of molecular medicine 医学-医学:研究与实验
CiteScore
12.30
自引率
0.00%
发文量
124
审稿时长
3 months
期刊介绍: The main aim of Spandidos Publications is to facilitate scientific communication in a clear, concise and objective manner, while striving to provide prompt publication of original works of high quality. The journals largely concentrate on molecular and experimental medicine, oncology, clinical and experimental cancer treatment and biomedical research. All journals published by Spandidos Publications Ltd. maintain the highest standards of quality, and the members of their Editorial Boards are world-renowned scientists.
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