使用米索前列醇联合低剂量γ辐射减轻大鼠百草枯诱导的肺损伤的前所未有的方法。

Unprecedented Approach for Using Misoprostol Alongside Low-Dose Gamma Radiation to Alleviate Paraquat-Induced Pulmonary Injury in Rats.

作者信息

Youssef Ahmed H, Mansour Heba H, Shousha Wafaa Gh, Galal Shereen M, Abdo Sara M

机构信息

Health Radiation Research Department, National Centre for Radiation Research & Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.

Department of Chemistry, Faculty of Science, Helwan University, Cairo, Egypt.

出版信息

Dose Response. 2025 Mar 25;23(1):15593258251326707. doi: 10.1177/15593258251326707. eCollection 2025 Jan-Mar.

DOI:10.1177/15593258251326707

PMID:40144808

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11938468/

Abstract

BACKGROUND

Abrupt inflammation and alveolar epithelial membrane damage, which may cause the alveolar membrane's malfunction, are related to acute lung injury (ALI). This could eventually lead to pulmonary fibrosis. While lung injury can happen in many ways, the current study will concentrate on the changes in lung pathology mediated by paraquat (PQ). Paraquat, a widely used herbicide, targets lung toxicity through inflammation and oxidative stress, which significantly contribute to lung damage.

OBJECTIVE

The current research was to ascertain whether low-dose gamma radiation (R) and misoprostol (MP) could lessen the lung inflammatory cascade started by PQ injection in rats.

METHODS

The ALI model was induced by I.P. injection of PQ (20 mg/kg once), and then treatment was done by MP and/or R for 14 days, and finally, the biochemical and histological parameters were measured in the lung tissues.

RESULTS

Our data suggest that PQ can promote ALI through TGF-β/smad, Notch, NF-κB, and ET-1 signaling pathways, resulting in EMT. These suggestions were supported by increased levels of TGF-β, inflammatory cytokines, α-SMA, NF-κB, ET-1, CTGF protein, and LPA, whereas PPAR-γ decreased. The aforementioned results have been confirmed by lung histopathology.

CONCLUSION

We suggest that the pulmonary inflammatory cascade was hindered and all the previously described gauges improved with R and/or MP therapy.

摘要

背景

急性肺损伤（ALI）与突然发生的炎症及肺泡上皮膜损伤有关，这可能导致肺泡膜功能障碍，最终可能导致肺纤维化。虽然肺损伤可通过多种方式发生，但本研究将专注于百草枯（PQ）介导的肺病理学变化。百草枯是一种广泛使用的除草剂，通过炎症和氧化应激导致肺毒性，这对肺损伤有显著影响。

目的

本研究旨在确定低剂量γ辐射（R）和米索前列醇（MP）是否能减轻大鼠注射PQ引发的肺部炎症级联反应。

方法

通过腹腔注射PQ（20mg/kg，单次）诱导ALI模型，然后用MP和/或R进行治疗14天，最后测量肺组织中的生化和组织学参数。

结果

我们的数据表明，PQ可通过TGF-β/smad、Notch、NF-κB和ET-1信号通路促进ALI，导致上皮-间质转化（EMT）。TGF-β、炎性细胞因子、α-SMA、NF-κB、ET-1、结缔组织生长因子（CTGF）蛋白和溶血磷脂酸（LPA）水平升高，而过氧化物酶体增殖物激活受体γ（PPAR-γ）降低，支持了上述观点。肺组织病理学证实了上述结果。