肝性脑病（HE）是最常见和最严重的肝脏和大脑疾病之一，其中氧化、炎症和凋亡轨迹的升级在病理上将急性肝损伤与神经损伤联系起来。 Mirabegron (Mira) 是一种 β3 肾上腺素受体激动剂，具有经证实的抗氧化和抗炎活性。目前的研究旨在探索 Mira 对硫代乙酰胺 (TAA) 诱导的大鼠 HE 的肝脏和神经保护作用。将大鼠分为三个实验组：正常对照组、TAA组，接受TAA（200mg/kg/天，连续三天），Mira治疗组接受Mira（10mg/kg/天，口服灌胃）连续15天，实验期第13天至第15天TAA中毒。米拉可以抵消高氨血症，增强大鼠的运动能力和运动协调性。它通过其抗氧化、抗凋亡和抗炎潜力减轻肝脏/神经损伤。 Mira 通过下调 p S536-核因子 kappa B p65 (p S536 NF) 主要靶向环磷酸腺苷 (cAMP)/磷酸化细胞外信号调节激酶 (p-Erk1/2)/过氧化物酶体增殖物激活受体 γ (PPARγ) 依赖性途径-κB p 65)/肿瘤坏死α (TNF-α)轴。同时，它还通过上调脑 cAMP/PPAR-γ/p-ERK1/2 和 p-CREB/BDNF/TrkB 以及减少GFAP 免疫反应性。 Mira 通过抑制 Bax 免疫反应性和升高 Bcl2 表现出抗凋亡活性。总而言之，Mira 除了上调神经保护信号通路外，还通过屏蔽抗氧化防御、减轻病理炎症和凋亡轴，对 TAA 诱导的大鼠 HE 表现出肝脏和神经保护作用。版权所有 © 2024。由 Elsevier Inc. 出版。

Hepatic encephalopathy (HE) is one of the most prevalent and severe hepatic and brain disorders in which escalation of the oxidative, inflammatory, and apoptotic trajectories pathologically connects acute liver injury with neurological impairment. Mirabegron (Mira) is a beta3 adrenergic receptor agonist with proven antioxidant and anti-inflammatory activity. The current research pointed to exploring Mira's hepato-and neuroprotective impacts against thioacetamide (TAA)-induced HE in rats. Rats were distributed into three experimental groups: the normal control group, the TAA group, received TAA (200 mg/kg/day for three consecutive days) and the Mira-treated group received Mira (10 mg/kg/day; oral gavage) for 15 consecutive days and intoxicated with TAA from the 13th to the 15th day of the experimental period. Mira counteracted hyperammonemia, enhanced rats' locomotor capability and motor coordination. It attenuated hepatic/neurological injuries by its antioxidant, anti-apoptotic as well as anti-inflammatory potentials. Mira predominantly targeted cyclic adenosine monophosphate (cAMP)/phosphorylated extracellular signal-regulated kinase (p-Erk1/2)/peroxisome proliferator-activated receptor gamma (PPARγ) dependent pathways via downregulation of p S536-nuclear factor kappa B p65 (p S536 NF-κB p 65)/tumor necrosis alpha (TNF-α) axis. Meanwhile, it attenuated nuclear factor erythroid 2-related factor (Nrf2) depletion in parallel with restoring of the neuroprotective defensive pathway by upregulation of cerebral cAMP/PPAR-γ/p-ERK1/2 and p-CREB/BDNF/TrkB besides reduction of GFAP immunoreactivity. Mira showed anti-apoptotic activity through inhibition of Bax immunoreactivity and elevation of Bcl2. To summarize, Mira exhibited a hepato-and neuroprotective effect against TAA-induced HE in rats via shielding antioxidant defense and mitigation of the pathological inflammatory and apoptotic axis besides upregulation of neuroprotective signaling pathways.Copyright © 2024. Published by Elsevier Inc.