Neurotensin via Type I Receptor Modulates the Endotoxemia Induced Oxido-Inflammatory Stress on the Sympathetic Adrenomedullary System of Mice Regulating NF-κβ/Nor-Epinephrine Pathway

IF 2.5 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Cell Biochemistry and Biophysics Pub Date : 2025-01-29 DOI:10.1007/s12013-025-01679-5

Asheesh Kumar Tiwari, Banalata Mohanty

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Abstract

The present study investigated the role of the neurotensin/NTS in the modulation of the lipopolysaccharide/LPS induced dysfunction of the sympatho-adrenal-medullary system/SAM using both the NTS receptor 1/NTSR₁ agonist PD149163/PD and antagonist SR48692 /SR. Forty eight mice were maintained in eight groups; Group I/control, Groups II, III, IV, and VII received LPS for 5 days further Group III/IV/VII received PD low dose/PD_L, PD high dose /PD_H and SR for 28 days respectively. Group V/VI received similar only PD_L and PD_H dose respectively whereas Group VIII was exposed to only SR for 28 days. Adrenal tissues histopathology examined through hematoxylin-eosin staining. The plasma levels of pro-inflammatory mediators (NF-kβ, TNF-α, IL-6), IL-10, corticosterone/CORT, nor-epinephrine/NE and NTS were assessed through ELISA. Biochemical detection was adopted to check the level of oxidative stress, assessed by measuring the thiobarbituric acid reactive substance/TBARS, superoxide dismutase/SOD and catalase/CAT in adrenal tissue to determine the therapeutic effect of NTS receptor 1 analogs. Compared with LPS group, PD ameliorated the adrenal medulla histopathology by significantly decreasing pro-inflammatory mediators, CORT and NE as well as enhancing IL-10, normalizing NTS level via down-regulating NF-κβ level. PD inhibited the oxidative stress in SAM system of adrenal by reducing TBARS, while enhancing SOD and CAT activity via regulating the CORT and NE levels. Conversely, SR administration could not normalize the deleterious effect caused by the LPS due to up-regulation of NF-κβ level. Therefore, PD ameliorates the inflammation and oxidative stress of SAM system by inhibiting NF-kβ/NE signaling pathway. Thus, PD could be used as a biological tool in SAM dysfunction for therapeutic evaluation of chronic inflammatory diseases.

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神经紧张素通过I型受体调节内毒素血症诱导的小鼠交感肾上腺髓系统氧化炎症应激调节NF-κβ/去甲肾上腺素通路

本研究利用NTS受体1/NTSR1激动剂PD149163/PD和拮抗剂SR48692 /SR，研究了神经紧张素/NTS在脂多糖/LPS诱导的交感神经-肾上腺-髓质系统/SAM功能障碍中的调节作用。将48只小鼠分为8组；组I/对照组、组II、组III、组IV和组VII继续给予LPS治疗5 d，组III/IV/VII分别给予PD低剂量/PDL、PD高剂量/PDH和SR治疗28 d。V/VI组分别仅接受相似剂量的PDL和PDH，而VIII组仅暴露于SR 28天。苏木精-伊红染色检查肾上腺组织病理学。采用ELISA法检测血浆促炎介质（NF-kβ、TNF-α、IL-6）、IL-10、皮质酮/CORT、去甲肾上腺素/NE、NTS水平。采用生化检测检测氧化应激水平，通过测定肾上腺组织中硫代巴比妥酸反应物质/TBARS、超氧化物歧化酶/SOD、过氧化氢酶/CAT来评估NTS受体1类似物的治疗效果。与LPS组相比，PD通过显著降低促炎介质、CORT和NE，提高IL-10，通过下调NF-κβ水平使NTS水平正常化，改善肾上腺髓质组织病理学。PD通过降低TBARS抑制肾上腺SAM系统的氧化应激，同时通过调节CORT和NE水平提高SOD和CAT活性。相反，SR不能通过上调NF-κβ水平来缓解LPS的不良影响。因此，PD通过抑制NF-kβ/NE信号通路改善SAM系统的炎症和氧化应激。因此，PD可作为SAM功能障碍的生物学工具，用于慢性炎症性疾病的治疗评价。

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来源期刊

Cell Biochemistry and Biophysics 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

7.5 months

期刊介绍： Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.