The immunomodulatory mechanism of brain injury induced by hyperhomocysteinemia in spontaneously hypertensive rats

摘要

Abstract Background Elevated plasma homocysteine (Hcy) concentration is considered as the diagnostic criteria of Hyperhomocysteinemia (HHcy), which is associated with the inflammatory response and blood‐brain barrier disruption. Previous studies have proposed that HHcy with hypertension was associated with the brain injury by enhancing the cerebrovascular permeability, however, the immune mechanism remains obscure. The purpose of the study is to explore the immunomodulatory mechanism of brain injury in spontaneously hypertensive rats (SHRs) induced by HHcy. Materials and methods Sixty SHRs were randomly assigned to three groups: SHR‐C (control group), SHR‐M (methionine group) and SHR‐T (treatment group). Physical examination of body weight, systolic blood pressure (SBP) and plasma Hcy content was measured every 4 weeks. Besides, T‐helper cell 17 and regulatory T cells (Treg)‐related inflammatory cytokines (interleukin [IL]‐6, IL‐17, IL‐10, and transforming growth factor beta [TGF‐β]) and genes (RORγt and FoxP3) were detected by enzyme‐linked immunosorbent assay, quantitative polymerase chain reaction , Western blot, and immunohistochemistry. Results High methionine diet could cause weight loss, SBP rising, and plasma Hcy content significantly elevated. IL‐16 and IL‐17A levels in peripheral blood and in brain tissue both lifted, while IL‐10 and TGF‐β levels dropped; RORγt expression raised in brain, nevertheless, FoxP3 levels were the opposite. After the intervention with vitamin B6, B12, and folic acid in SHR‐T group, these trends would be eased or completely changed. Furthermore, brain tissue slices showed that IL‐17‐positive cells tended to decrease, and IL‐10‐positive cells increased in SHR‐T group, which was reversed in SHR‐M group. Conclusions HHcy may promote inflammation that can lead to brain lesions and down‐regulate immune response to protect the brain.