Methyl badosolone reduces oxidative stress and inflammatory response in rats with traumatic brain injury by activating Nrf2/HO-1
10.3760/cma.j.issn.1671-0282.2025.02.011
- VernacularTitle:甲基巴多索隆通过激活Nrf2/HO-1减轻创伤性脑损伤大鼠氧化应激和炎症反应
- Author:
Chengjian LI
1
;
Lanjuan XU
;
Tingting AN
;
Jing LIU
;
Qiong WU
;
Jie JIN
;
Huihui DING
;
Yifan MA
;
Xiangyang LI
;
Baohui JIA
Author Information
1. 郑州大学附属郑州中心医院重症医学科，郑州 450001
- Keywords:
Traumatic brain injury;
Methyl badosolone;
Oxidative stress;
Inflammation;
Nuclear factor erythroid2 related factor 2
- From:
Chinese Journal of Emergency Medicine
2025;34(2):200-207
- CountryChina
- Language:Chinese
-
Abstract:
Objective:Explore the protective effect and mechanism of methyl badosolone (CDDO-Me) on rats with traumatic brain injury (TBI).Methods:A total of 72 SPF-grade SD rats aged 8 weeks were randomly (random number) divided into 4 groups ( n=18) using the random number table method: Sham, TBI, TBI+Vehicle, and TBI+CDDO-Me. The rat TBI model was established using the hydraulic impact head injury method. The TBI+CDDO-Me group was administered CDDO-Me (dissolved in 1% DMSO, at a dose of 10 mg/kg) via intraperitoneal injection 30 minutes after modeling, twice a day for a total of 3 days. On the third day after modeling, brain tissue was collected for pathological and water content detection after mNSS scoring. Immunofluorescence double staining was used to detect the expression of nuclear factor erythroid2 related factor 2 (Nrf2); immunohistochemical staining was used to detect the expression of ionized calcium binding adapter molecule-1(Iba-1); ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α), interleukin (IL)-1β, and IL-18 in serum; kits were used to detect the levels of malondialdehyde (MDA) and reactive oxygen species (ROS); Western blot was used to detect the expression of the Nrf2 pathway, B-cell lymphoma-2 (BCL-2), and BCL-2 associated X protein (BAX). Results:(1) Compared with the Sham group, the mNSS scores and water content in the injured cortex of the TBI group rats were significantly increased (both P<0.05), and both significantly decreased after CDDO-Me intervention (both P<0.05). (2) Compared with the Sham group, the proportion of Nissl-stained injured neurons and apoptotic positive cells in the TBI group rats were significantly increased (both P<0.05), and both significantly decreased after CDDO-Me intervention (both P<0.05), accompanied by a decrease in BAX protein expression and upregulation of BCL-2 protein expression (both P<0.05). (3) Immunofluorescence and Western blot results showed that compared with the Sham group, the expression of total Nrf2, nuclear Nrf2, HO-1, and NQO1 proteins in the TBI group were all increased (all P<0.05), and the increase was more significant after CDDO-Me intervention (all P<0.05). (4) Immunohistochemistry and ELISA results showed that compared with the Sham group, the levels of MDA, ROS, Iba-1 in brain tissue and the levels of TNF-α, IL-1β, and IL-18 in serum in the TBI group rats were all significantly increased (all P<0.05), and all significantly decreased after CDDO-Me intervention (all P<0.05). Conclusion:CDDO-Me helps to reduce oxidative stress and inflammatory responses in TBI rats, and the mechanism may be related to the activation of the Nrf2/HO-1 antioxidant stress pathway.
