From Bench to Bedside: Eupatilin Activates Antioxidant Defenses and Reduces Fibrosis in Experimental Cholestasis.

IF 1.4 3区 医学 Q2 PEDIATRICS
Wei-Lu Wang, Yan Chen, Paul Kwong Hang Tam
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Abstract

The aim of this study is to explore the protective effects and mechanisms of Eupatilin, a peroxisome proliferator-activated receptor α (PPARα) agonist, on cholestatic liver disease induced by common bile duct ligation (BDL) in mice.We selected Balb/c mice (both male and female) aged 6 to 8 weeks for the common BDL procedure (ethical approval number: MUST-FDCT-20241114001). The groups include the BDL group and the BDL+ Eupatilin group, with three mice in each group. Once the mice developed jaundice postsurgery (5 days), they were treated with Eupatilin via gavage at a dosage of 20 mg/kg daily for a period of 8 days. On day 13, ocular blood was collected, and liver tissues were extracted for histopathological examination with H&E staining, Sirius Red staining, and subsequent RNA sequencing. Statistical differences among the parameters were evaluated using a t-test.Eupatilin reduces the liver weight/body weight ratio by 41% and ameliorates liver necrosis and fibrosis in Balb/c mice. It could decrease alanine transaminase ( p = 0.0498), aspartate aminotransferase (p = 0.0077), while maintaining ALB (Albumin) and γ-GT (gamma-glutamyl transferase) within normal ranges. RNA sequencing analysis revealed that antioxidant genes (acetaldehyde dehydrogenase 2 [Aldh2] and superoxide dismutase 1 [Sod1]) might be the targets of Eupatilin action.We found that Eupatilin can upregulate antioxidant genes (Aldh2; p = 0.0107) and Sod1 (p = 0.0208) of Balb/c mice, thereby ameliorating BDL damage in mice with cholestatic liver disease.

从实验室到床边:尤帕替林激活抗氧化防御和减少实验性胆汁淤积的纤维化。
本研究旨在探讨过氧化物酶体增殖物激活受体α (PPARα)激动剂乌帕替林对胆总管结扎(BDL)所致小鼠胆汁淤积性肝病的保护作用及其机制。我们选择6 ~ 8周龄的Balb/c小鼠(雄性和雌性)进行普通BDL手术(伦理批准号:MUST-FDCT-20241114001)。分为BDL组和BDL+ Eupatilin组,每组3只。术后(5 d)小鼠出现黄疸后,以20 mg/kg /天的剂量灌胃尤帕替林,连续8天。第13天,取眼血,取肝组织进行组织病理学检查,采用H&E染色、Sirius Red染色,并进行RNA测序。参数间的统计差异采用t检验。尤帕替林使Balb/c小鼠的肝重/体重比降低41%,并改善肝坏死和纤维化。可降低丙氨酸转氨酶(p = 0.0498)、天冬氨酸转氨酶(p = 0.0077),维持ALB(白蛋白)和γ-GT (γ-谷氨酰转移酶)在正常范围内。RNA测序分析显示抗氧化基因(乙醛脱氢酶2 [Aldh2]和超氧化物歧化酶1 [Sod1])可能是Eupatilin作用的靶点。我们发现乌帕替林可以上调Balb/c小鼠的抗氧化基因(Aldh2; p = 0.0107)和Sod1 (p = 0.0208),从而改善胆汁淤积性肝病小鼠的BDL损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.90
自引率
5.60%
发文量
66
审稿时长
6-12 weeks
期刊介绍: This broad-based international journal updates you on vital developments in pediatric surgery through original articles, abstracts of the literature, and meeting announcements. You will find state-of-the-art information on: abdominal and thoracic surgery neurosurgery urology gynecology oncology orthopaedics traumatology anesthesiology child pathology embryology morphology Written by surgeons, physicians, anesthesiologists, radiologists, and others involved in the surgical care of neonates, infants, and children, the EJPS is an indispensable resource for all specialists.
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