Babu Gyan, Mohanty Banalata
Department of Zoology, University of Allahabad, Prayagraj, Uttar Pradesh 211002, India.
Department of Zoology, University of Allahabad, Prayagraj, Uttar Pradesh 211002, India.
Neuropeptides. 2023 Feb;97:102297. doi: 10.1016/j.npep.2022.102297. Epub 2022 Oct 25.
Lipopolysaccharide (LPS), a toxic component of the cell wall of Gram-negative bacteria, is a potent immune stressor. LPS-induced inflammation of the gut-liver axis is well demonstrated. Neurotensin (NTS), a tri-decapeptide present in the gastrointestinal tract, has anti-inflammatory, anti-oxidative, and growth-promoting properties. This study elucidated the efficacy of PD149163, the type I NTS receptor agonist (NTS) in the modulation of LPS-induced inflammation of the gut-liver axis of mice. Young-adult female mice (Age: 8 weeks; BW: 25 ± 2.5 g) were maintained in six groups (6/group); Group I as control and Group II, III & IV were exposed to LPS (1 mg/kg BW/Day; i.p.) for five days. LPS pre-exposed Group III and Group IV mice were treated with NTS agonist PD149163 (100 μg/kg BW i.p.) and antagonist SR48692 (0.5 mg/kg BW i.p.) respectively for 28 days. Group V and Group VI mice were exposed to only PD149163 and only SR48692 respectively with the doses as mentioned above for 28 days. Group I and LPS-exposed Group II mice were also maintained four weeks without further treatment. Histopathology revealed LPS-induced inflammation of the gut and liver. Significant elevation of plasma TNF-α and IL-6 and serum ALT and AST reflected as biomarkers of inflammation. Oxidative stress on both organs was distinct from decreased glutathione reductase and increased lipid peroxidation. PD149163 but not SR48692 ameliorated LPS-induced inflammation in both gut and liver counteracting inflammatory responses and oxidative stress. The use of NTS agonists including PD149163 could be exploited for therapeutic intervention of inflammatory diseases including that of the gut-liver axis.
脂多糖（LPS）是革兰氏阴性菌细胞壁的一种毒性成分，是一种强大的免疫应激源。LPS诱导的肠-肝轴炎症已得到充分证实。神经降压素（NTS）是一种存在于胃肠道的十三肽，具有抗炎、抗氧化和促进生长的特性。本研究阐明了I型NTS受体激动剂PD149163对LPS诱导的小鼠肠-肝轴炎症的调节作用。将年轻成年雌性小鼠（年龄：8周；体重：25±2.5克）分为六组（每组6只）；第一组作为对照组，第二、三、四组连续五天腹腔注射LPS（1毫克/千克体重/天）。LPS预处理的第三组和第四组小鼠分别用NTS激动剂PD149163（100微克/千克体重腹腔注射）和拮抗剂SR48692（0.5毫克/千克体重腹腔注射）治疗28天。第五组和第六组小鼠分别仅接受上述剂量的PD149163和SR48692治疗28天。第一组和接受LPS处理的第二组小鼠也在不进行进一步治疗的情况下维持四周。组织病理学显示LPS诱导的肠道和肝脏炎症。血浆TNF-α和IL-6以及血清ALT和AST显著升高，反映为炎症生物标志物。两个器官的氧化应激表现为谷胱甘肽还原酶降低和脂质过氧化增加。PD149163而非SR48692减轻了LPS诱导的肠道和肝脏炎症，抵消了炎症反应和氧化应激。包括PD149163在内的NTS激动剂可用于炎症性疾病的治疗干预，包括肠-肝轴疾病。
