Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
Department of Neurology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
J Neuroimmunol. 2023 Feb 15;375:578013. doi: 10.1016/j.jneuroim.2022.578013. Epub 2022 Dec 26.
Neuroinflammation is a significant contributor to post-ischemic neuronal death after stroke, and Toll-Like Receptors (TLRs) are one of the essential mediators in many inflammatory pathways. TLRs activate the nuclear factor kappa β (NF-kβ), which promotes the expression of various pro-inflammatory genes such as interleukin (IL-1β) and IL-6. 1,25(OH)2D3, also known as calcitriol, is an active form of vitamin D3 that acts as a neurosteroid compound with anti-inflammatory properties. This study aimed to determine the modulatory effects of calcitriol hormone on post-ischemic immunity response.
Neurological tests and conventional blood factors were evaluated in patients with stroke symptoms upon arrival (n = 38) to confirm the stroke. A blood sample was taken from each stroke patient immediately upon admission and again after 24 h. The experimental group was given 10 μg calcitriol orally. The gene expression levels of TLR4, TLR2, NF-kβ, IL-1β, and IL-6 pro-inflammatory factors were measured using real-time PCR. The protein expression of TLR4 and NF-kβ markers was assessed using the flow cytometry technique.
TLR4, NF-kβ, and pro-inflammatory factors IL-1β and IL-6 expression increased significantly after an ischemic stroke, and calcitriol could modulate the TLR4/NF-kβ signaling pathway 24 h after ischemia.
Calcitriol may be considered a protective reagent after ischemia by reducing the TLR4/NF-kB activation cascade and probably plays a beneficial role in reducing and improving ischemic stroke patients' symptoms.
Iranian Registry of Clinical Trials identifier: IRCT2017012532174N1.
神经炎症是中风后缺血性神经元死亡的一个重要因素，而 Toll 样受体 (TLR) 是许多炎症途径中的重要介质之一。TLR 激活核因子 kappa β (NF-kβ)，促进白细胞介素 (IL-1β) 和 IL-6 等各种促炎基因的表达。1,25(OH)2D3，也称为钙三醇，是维生素 D3 的一种活性形式，作为一种具有抗炎特性的神经甾体化合物发挥作用。本研究旨在确定钙三醇激素对缺血后免疫反应的调节作用。
对有中风症状的患者进行神经学测试和常规血液因子评估（n=38）以确认中风。每位中风患者入院时立即采集一份血样，24 小时后再次采集。实验组给予 10μg 钙三醇口服。使用实时 PCR 测量 TLR4、TLR2、NF-kβ、IL-1β 和 IL-6 促炎因子的基因表达水平。使用流式细胞术技术评估 TLR4 和 NF-kβ 标志物的蛋白表达。
缺血性中风后 TLR4、NF-kβ 和促炎因子 IL-1β 和 IL-6 的表达显著增加，钙三醇可在缺血后 24 小时调节 TLR4/NF-kβ 信号通路。
钙三醇通过减少 TLR4/NF-kB 激活级联反应，可能被认为是缺血后的保护试剂，并可能在减轻和改善缺血性中风患者的症状方面发挥有益作用。
伊朗临床试验注册中心标识符：IRCT2017012532174N1。
