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姜黄素通过Nrf-2/HO-1信号通路改善雨蛙肽诱导的慢性胰腺炎。

Curcumin ameliorates cerulein‑induced chronic pancreatitis through Nrf‑2/HO‑1 signaling.

作者信息

Kim Dong-Uk, Kweon Bitna, Oh Jin-Young, Noh Gyeong-Ran, Lim Yebin, Yu Jihyun, Kim Myoung-Jin, Kim Dong-Gu, Park Sung-Joo, Bae Gi-Sang

机构信息

Department of Pharmacology, School of Korean Medicine, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea.

Department of Herbology, School of Korean Medicine, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea.

出版信息

Mol Med Rep. 2025 May;31(5). doi: 10.3892/mmr.2025.13501. Epub 2025 Mar 27.

Abstract

Chronic pancreatitis (CP) is an invasive inflammatory disorder characterized by endocrine and exocrine dysfunction. There are currently no effective drugs for the treatment of CP. The present study investigated whether curcumin improves cerulein‑induced CP fibrosis in a mouse model and pancreatic stellate cells (PSCs). The CP mouse model was established by intraperitoneally injecting cerulein (50 µg/kg) for 3 weeks (six times at 1 h intervals/day; 4 days/week). To investigate the effects of curcumin, dimethyl sulfoxide or curcumin was injected intraperitoneally 1 h before the first daily injection of cerulein. To determine the severity of CP, the pancreas was harvested 24 h after the last cerulein injection for histological examination and assessment of PSC activation and collagen deposition. Additionally, levels of the nuclear factor erythroid 2‑related factor 2 (Nrf2) and heme oxygenase‑1 (HO‑1) were evaluated to determine the mechanism underlying the anti‑fibrotic effect of curcumin in PSCs. Curcumin improved pancreatic injury associated with CP by inhibiting PSC activation and collagen deposition. Moreover, curcumin increased HO‑1 expression levels via the activation of Nrf2 in PSCs, which suppressed the activation of PSCs. In conclusion, the present results suggest that curcumin can ameliorate pancreatic fibrosis induced by repetitive cerulein challenges via the induction of HO‑1 and is a beneficial agent for the treatment of CP.

摘要

慢性胰腺炎(CP)是一种以内分泌和外分泌功能障碍为特征的侵袭性炎症性疾病。目前尚无治疗CP的有效药物。本研究调查了姜黄素是否能改善小鼠模型和胰腺星状细胞(PSC)中雨蛙肽诱导的CP纤维化。通过腹腔注射雨蛙肽(50μg/kg)3周(每天1小时间隔注射6次;每周4天)建立CP小鼠模型。为了研究姜黄素的作用,在每天首次注射雨蛙肽前1小时腹腔注射二甲基亚砜或姜黄素。为了确定CP的严重程度,在最后一次注射雨蛙肽后24小时采集胰腺进行组织学检查,并评估PSC激活和胶原沉积情况。此外,评估核因子红细胞2相关因子2(Nrf2)和血红素加氧酶-1(HO-1)的水平,以确定姜黄素在PSC中抗纤维化作用的潜在机制。姜黄素通过抑制PSC激活和胶原沉积改善与CP相关的胰腺损伤。此外,姜黄素通过激活PSC中的Nrf2增加HO-1表达水平,从而抑制PSC的激活。总之,目前的结果表明,姜黄素可通过诱导HO-1改善反复雨蛙肽刺激诱导的胰腺纤维化,是治疗CP的有益药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/842c/11963747/c53f976c265a/mmr-31-05-13501-g00.jpg

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