Preliminary analysis of immunoregulatory mechanism of hyperhomocysteinemia‑induced brain injury in Wistar‑Kyoto rats

Zhang,Yu; Wang,Lin; Li,Xin; Geng,Jie

doi:10.3892/etm.2021.9914

Preliminary analysis of immunoregulatory mechanism of hyperhomocysteinemia‑induced brain injury in Wistar‑Kyoto rats

Authors:
- Yu Zhang
- Lin Wang
- Xin Li
- Jie Geng
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Affiliations: 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
Published online on: March 16, 2021 https://doi.org/10.3892/etm.2021.9914
Article Number: 483
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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