PMID- 33790992
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210402
IS  - 1792-0981 (Print)
IS  - 1792-1015 (Electronic)
IS  - 1792-0981 (Linking)
VI  - 21
IP  - 5
DP  - 2021 May
TI  - Preliminary analysis of immunoregulatory mechanism of 
      hyperhomocysteinemia-induced brain injury in Wistar-Kyoto rats.
PG  - 483
LID - 10.3892/etm.2021.9914 [doi]
LID - 483
AB  - 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-beta, associated 
      with T helper cell 17 (Th17) and regulatory T (Treg) cells and key regulator 
      genes, including retinoic acid-related orphan receptor gamma t (RORgammat) 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 RORgammat 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.
CI  - Copyright: (c) Zhang et al.
FAU - Zhang, Yu
AU  - Zhang Y
AD  - Department of Geriatrics, The Second Hospital of Tianjin Medical University, 
      Tianjin 300211, P.R. China.
FAU - Wang, Lin
AU  - Wang L
AD  - Department of Geriatrics, The Second Hospital of Tianjin Medical University, 
      Tianjin 300211, P.R. China.
FAU - Li, Xin
AU  - Li X
AD  - Department of Geriatrics, The Second Hospital of Tianjin Medical University, 
      Tianjin 300211, P.R. China.
FAU - Geng, Jie
AU  - Geng J
AD  - Department of Cardiology, Tianjin Chest Hospital, Tianjin 300211, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20210316
PL  - Greece
TA  - Exp Ther Med
JT  - Experimental and therapeutic medicine
JID - 101531947
PMC - PMC8005698
OTO - NOTNLM
OT  - brain injury
OT  - homocysteine
OT  - hyperhomocysteinemia
OT  - immune imbalance
COIS- The authors declare that they have no competing interests.
EDAT- 2021/04/02 06:00
MHDA- 2021/04/02 06:01
PMCR- 2021/03/16
CRDT- 2021/04/01 06:27
PHST- 2020/08/02 00:00 [received]
PHST- 2021/02/05 00:00 [accepted]
PHST- 2021/04/01 06:27 [entrez]
PHST- 2021/04/02 06:00 [pubmed]
PHST- 2021/04/02 06:01 [medline]
PHST- 2021/03/16 00:00 [pmc-release]
AID - ETM-0-0-09914 [pii]
AID - 10.3892/etm.2021.9914 [doi]
PST - ppublish
SO  - Exp Ther Med. 2021 May;21(5):483. doi: 10.3892/etm.2021.9914. Epub 2021 Mar 16.