载多西环素的磷酸钙纳米粒子具有果胶涂层，可通过增强 AMPK 来减轻脂多糖诱导的神经炎症。

Doxycycline-Loaded Calcium Phosphate Nanoparticles with a Pectin Coat Can Ameliorate Lipopolysaccharide-Induced Neuroinflammation Via Enhancing AMPK.

机构信息

Clinical Pharmacology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

Medical Biochemistry Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

出版信息

J Neuroimmune Pharmacol. 2024 Jan 18;19(1):2. doi: 10.1007/s11481-024-10099-w.

DOI:10.1007/s11481-024-10099-w

PMID:38236457

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10796490/

Abstract

Neuroinflammation occurs in response to different injurious triggers to limit their hazardous effects. However, failure to stop this process can end in multiple neurological diseases. Doxycycline (DX) is a tetracycline, with potential antioxidant and anti-inflammatory properties. The current study tested the effects of free DX, DX-loaded calcium phosphate (DX@CaP), and pectin-coated DX@CaP (Pec/DX@CaP) nanoparticles on the lipopolysaccharide (LPS)-induced neuroinflammation in mice and to identify the role of adenosine monophosphate-activated protein kinase (AMPK) in this effect. The present study was conducted on 48 mice, divided into 6 groups, eight mice each. Group 1 (normal control), Group 2 (blank nanoparticles-treated), Group 3 (LPS (untreated)), Groups 4, 5, and 6 received LPS, then Group 4 received free DX, Group 5 received DX-loaded calcium phosphate nanoparticles (DX@CaP), and Group 6 received DX-loaded calcium phosphate nanoparticles with a pectin coat (Pec/DX@CaP). At the end of the experimentation period, behavioral tests were carried out. Then, mice were sacrificed, and brain tissue was extracted and used for histological examination, and assessment of interleukin-6 positive cells in different brain areas, in addition to biochemical measurement of SOD activity, TLR-4, AMPK and Nrf2. LPS can induce prominent neuroinflammation. Treatment with (Pec/DX@CaP) can reverse most behavioral, histopathological, and biochemical changes caused by LPS. The findings of the current study suggest that (Pec/DX@CaP) exerts a significant reverse of LPS-induced neuroinflammation by enhancing SOD activity, AMPK, and Nrf2 expression, in addition to suppression of TLR-4.

摘要

神经炎症是对不同损伤触发因素的反应，以限制其有害影响。然而，如果这个过程不能停止，就可能导致多种神经疾病。多西环素（DX）是一种四环素，具有潜在的抗氧化和抗炎特性。本研究测试了游离 DX、负载 DX 的磷酸钙（DX@CaP）和果胶包裹的 DX@CaP（Pec/DX@CaP）纳米颗粒对小鼠脂多糖（LPS）诱导的神经炎症的影响，并确定了腺苷单磷酸激活蛋白激酶（AMPK）在这一作用中的作用。本研究在 48 只小鼠上进行，分为 6 组，每组 8 只。第 1 组（正常对照组），第 2 组（空白纳米颗粒处理组），第 3 组（未处理 LPS 组），第 4、5 和 6 组给予 LPS，然后第 4 组给予游离 DX，第 5 组给予负载 DX 的磷酸钙纳米颗粒（DX@CaP），第 6 组给予负载 DX 的磷酸钙纳米颗粒与果胶涂层（Pec/DX@CaP）。实验结束时，进行行为测试。然后处死小鼠，提取脑组织进行组织学检查，并评估不同脑区白细胞介素-6 阳性细胞，以及 SOD 活性、TLR-4、AMPK 和 Nrf2 的生化测定。LPS 可诱导明显的神经炎症。（Pec/DX@CaP）的治疗可以逆转 LPS 引起的大多数行为、组织病理学和生化变化。本研究结果表明，（Pec/DX@CaP）通过增强 SOD 活性、AMPK 和 Nrf2 的表达，以及抑制 TLR-4，对 LPS 诱导的神经炎症具有显著的逆转作用。