Zhang Yu, Wang Lin, Li Xin, Geng Jie
Department of Geriatrics, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
Department of Cardiology, Tianjin Chest Hospital, Tianjin 300211, P.R. China.
Exp Ther Med. 2021 May;21(5):483. doi: 10.3892/etm.2021.9914. Epub 2021 Mar 16.
Hyperhomocysteinemia (HHcy) can be used as an independent risk factor for predicting cardiovascular disease, stroke and vitamin B12 deficiency. Patients with HHcy have elevated plasma homocysteine (Hcy) concentrations. Enhancing cerebrovascular permeability of substances such as Hcy and brain damage will synergistically increase the symptoms of hypertension, but the specific immune regulation mechanism is still not clear. The purpose of the present study was to preliminarily explore the immunomodulatory mechanism of brain damage caused by HHcy in Wistar-Kyoto (WKY) rats. A total of 60 WKYs were randomly divided into three groups: WKY control group (WKY-C group), WKY methionine group (WKY-M group) and WKY treatment group (WKY-T group; vitamin B6, B12 and folic acid were used as treatment), with 20 rats in each group. Physical examination of body weight, systolic blood pressure (SBP) and plasma Hcy content was performed routinely. The concentration of cytokines, including IL-6, IL-10, IL-17A and TGF-β, associated with T helper cell 17 (Th17) and regulatory T (Treg) cells and key regulator genes, including retinoic acid-related orphan receptor γ t (RORγt) and forkhead box P3 (FoxP3), were detected by ELISA, reverse transcription-quantitative PCR and western blotting. Th17/Treg lymphocytes were determined by flow cytometry. MRI scan was preliminarily used to detect the changes characteristic of the ischemic stroke. The results revealed that high methionine diets might have a significant effect on the body weight and SBP. The inflammatory response effect of Treg cells was significantly inhibited in the WKY-M group, and that of Th17 cells was upregulated when compared to the WKY-T group. Compared with the WKY-T group, the expression levels of IL-17A and RORγt in the WKY-M group were significantly upregulated, while the mRNA levels of FoxP3 in the WKY-M group were significantly downregulated. The diet intervention (including vitamins B6 and B12 and folic acid) could reduce the level of Hcy in the blood, but also reduce the inflammatory response and rectify the Treg/Th17 immune imbalance to ameliorate the brain tissue damage. In conclusion, the present study indicated that HHcy can promote inflammation by triggering Treg/Th17 immune imbalance to ameliorate the brain tissue damage.
高同型半胱氨酸血症（HHcy）可作为预测心血管疾病、中风和维生素B12缺乏的独立危险因素。HHcy患者的血浆同型半胱氨酸（Hcy）浓度升高。增强脑血管对Hcy等物质的通透性以及脑损伤会协同加重高血压症状，但具体的免疫调节机制仍不清楚。本研究的目的是初步探讨HHcy对Wistar-Kyoto（WKY）大鼠脑损伤的免疫调节机制。将60只WKY大鼠随机分为三组：WKY对照组（WKY-C组）、WKY蛋氨酸组（WKY-M组）和WKY治疗组（WKY-T组；使用维生素B6、B12和叶酸进行治疗），每组20只大鼠。常规进行体重、收缩压（SBP）和血浆Hcy含量的体格检查。通过酶联免疫吸附测定（ELISA）、逆转录定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法检测与辅助性T细胞17（Th17）和调节性T（Treg）细胞相关的细胞因子（包括白细胞介素6、白细胞介素10、白细胞介素17A和转化生长因子-β）的浓度以及关键调节基因（包括维甲酸相关孤儿受体γt（RORγt）和叉头框P3（FoxP3））。通过流式细胞术测定Th17/Treg淋巴细胞。初步使用磁共振成像（MRI）扫描检测缺血性中风的特征性变化。结果显示，高蛋氨酸饮食可能对体重和SBP有显著影响。与WKY-T组相比，WKY-M组中Treg细胞的炎症反应作用受到显著抑制，而Th17细胞的炎症反应作用上调。与WKY-T组相比，WKY-M组中白细胞介素17A和RORγt的表达水平显著上调，而WKY-M组中FoxP3的mRNA水平显著下调。饮食干预（包括维生素B6、B12和叶酸）可以降低血液中的Hcy水平，还可以减轻炎症反应并纠正Treg/Th17免疫失衡，以改善脑组织损伤。总之，本研究表明，HHcy可通过引发Treg/Th17免疫失衡促进炎症反应，从而改善脑组织损伤。
