Vitamin D Activates Nrf2 to Prevent Nerve Injury and Reduce Brain Damage in Acute Cerebral Infarction.

IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Hong-Min Zhao, Li-Qin Mu, Jing Wang, Run-Zhi Chen, Yang Li, Lin Zhao, Yu Zhao, Li-Na Liu
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引用次数: 0

Abstract

Objective: This study aimed to investigate the neuroprotective effects of cholecalciferol cholesterol emulsion (CCE), a vitamin D (VD) precursor, in a murine model of acute cerebral infarction (ACI) and to elucidate the role of the Nrf2 signaling pathway in mediating these effects.

Methods: Forty C57BL/6J mice (male and female) were divided into five groups (n = 10 per group): control, control + CCE, ACI, ACI + CCE, and ACI + CCE + ML385 (an Nrf2 inhibitor). ACI was induced by middle cerebral artery occlusion (MCAO). CCE was administered for three weeks prior to ACI induction, and ML385 was administered intravenously to inhibit Nrf2. Neurological function, brain edema, and infarct size, as well as inflammatory and apoptotic marker levels, were assessed post-ACI. Statistical analyses were conducted via one-way ANOVA and Student's t test, with P < 0.05 considered significant.

Results: Compared to ACI group, CCE significantly reduced neurological deficits, brain edema, and infarct size (P < 0.01). The ACI + CCE group presented improved short-term memory retention, as evidenced by shorter avoidance latency in shuttle avoidance tests (P < 0.01). CCE administration attenuated the expression of inflammatory markers (IL-6, MIF, Lp-PLA2) while increasing IL-10 levels (P < 0.001). Furthermore, CCE increased Nrf2 and HO-1 expression and reduced apoptosis by decreasing the Bax/Bcl-2 ratio in brain tissue (P < 0.001). ML385 abolished these neuroprotective effects, confirming the role of the Nrf2 pathway in mediating the benefits of VD.

Conclusion: VD, via VD receptor-mediated activation of the Nrf2/HO-1 pathway, reduces inflammation, apoptosis, and neurological damage following ACI. These findings support the therapeutic potential of VD in the treatment of ischemic stroke and highlight the importance of Nrf2 in mediating these effects.

维生素D激活Nrf2预防急性脑梗死的神经损伤和减少脑损伤。
目的:研究维生素D (VD)前体胆钙化醇-胆固醇乳剂(CCE)对急性脑梗死(ACI)小鼠模型的神经保护作用,并探讨Nrf2信号通路在其中的作用。方法:40只C57BL/6J小鼠(雄性和雌性)分为5组(每组10只):对照组、对照组+ CCE、ACI、ACI + CCE、ACI + CCE + ML385 (Nrf2抑制剂)。脑中动脉闭塞(MCAO)诱导ACI。ACI诱导前给予CCE 3周,ML385静脉给予抑制Nrf2。aci后评估神经功能、脑水肿、梗死面积以及炎症和凋亡标志物水平。结果:与ACI组相比,CCE显著减少了神经功能缺损、脑水肿和梗死面积(P结论:VD通过VD受体介导的Nrf2/HO-1通路的激活,减少了ACI后的炎症、细胞凋亡和神经损伤。这些发现支持了VD在缺血性卒中治疗中的治疗潜力,并强调了Nrf2在介导这些作用中的重要性。
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来源期刊
Current Medical Science
Current Medical Science Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
4.70
自引率
0.00%
发文量
126
期刊介绍: Current Medical Science provides a forum for peer-reviewed papers in the medical sciences, to promote academic exchange between Chinese researchers and doctors and their foreign counterparts. The journal covers the subjects of biomedicine such as physiology, biochemistry, molecular biology, pharmacology, pathology and pathophysiology, etc., and clinical research, such as surgery, internal medicine, obstetrics and gynecology, pediatrics and otorhinolaryngology etc. The articles appearing in Current Medical Science are mainly in English, with a very small number of its papers in German, to pay tribute to its German founder. This journal is the only medical periodical in Western languages sponsored by an educational institution located in the central part of China.
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