Tiwari Asheesh Kumar, Mohanty Banalata
Department of Zoology, University of Allahabad, Prayagraj, Uttar Pradesh, 211002, India.
Cell Biochem Biophys. 2025 Jan 29. doi: 10.1007/s12013-025-01679-5.
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/NTSR 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, PD high dose /PD and SR for 28 days respectively. Group V/VI received similar only PD and PD 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.
本研究使用神经降压素受体1（NTSR）激动剂PD149163（PD）和拮抗剂SR48692（SR），研究了神经降压素（NTS）在调节脂多糖（LPS）诱导的交感-肾上腺髓质系统（SAM）功能障碍中的作用。48只小鼠分为8组；第一组为对照组，第二、三、四和七组连续5天给予LPS，此外，第三、四、七组分别连续28天给予低剂量PD、高剂量PD和SR。第五、六组仅分别给予类似剂量的PD和PD，而第八组仅连续28天给予SR。通过苏木精-伊红染色检查肾上腺组织的组织病理学。通过酶联免疫吸附测定法（ELISA）评估促炎介质（NF-kβ、TNF-α、IL-6）、IL-10、皮质酮（CORT）、去甲肾上腺素（NE）和NTS的血浆水平。采用生化检测方法，通过测量肾上腺组织中的硫代巴比妥酸反应物质（TBARS）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）来检测氧化应激水平，以确定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水平，同时增强IL-10水平，并通过下调NF-κβ水平使NTS水平恢复正常，从而改善了肾上腺髓质的组织病理学。PD通过降低TBARS抑制肾上腺SAM系统中的氧化应激，同时通过调节CORT和NE水平增强SOD和CAT活性。相反，由于NF-κβ水平上调，给予SR不能使LPS引起的有害作用恢复正常。因此，PD通过抑制NF-kβ/NE信号通路改善了SAM系统的炎症和氧化应激。因此，PD可作为一种生物学工具，用于SAM功能障碍中慢性炎症性疾病的治疗评估。
