Fenofibrate treatment of rats with experimental autoimmune myocarditis by alleviating Treg/Th17 disorder.
OBJECTIVE
To investigate the curative effect of fenofibrate on rats with experimental autoimmune myocarditis (EAM) and its immunological mechanism.


METHODS
Twenty-four rats were equally randomised into three groups: an EAM group, fenofibrate group, and control group, then a subcutaneous injection of purified pig cardiac myosin was given to the EAM group rats and the fenofibrate group, while equivalent normal saline (NS) was given to the control group. After that, the fenofibrate group received fenofibrate by gavage (100 mg/kg/d) and equivalent NS was given to the other groups, lasting for 17 days. Then the rats were sacrificed in order to take heart tissues; HE staining and qRT-PCR method was used to assess the severity of heart failure and mRNA level of cytokines; NK-κB protein content was analyzed by Western-blot. Healthy rat spleen tissue was prepared for splenocyte suspension. Subsequently, splenocytes were administrated similarly to the test in vivo for detecting cytokine mRNA levels.


RESULTS
Compared with the control group, heart weight in EAM group was heavier than in the other groups (p < 0.05), and there was severe inflammatory cell infiltration in heart tissue of the EAM group. Th17 cell-related cytokines mRNA levels in the EAM group/induction group were evidently higher than in other groups (p < 0.05); FOX-p3 mRNA level in the EAM group/induction group was lower than other groups, mRNA levels of IL-10 and FOX-p3 in the fenofibrate group were higher than in the EAM group/induction group (p < 0.05). Fenofibrate could significantly inhibit the up-regulation of NF-κB protein in EAM rats (p < 0.05).


CONCLUSIONS
By inhibiting the development of Th17 cells and promoting the differentiation of Tregs, fenofibrate alleviated Treg/Th17 disorder and inhibited inflammation in rats with EAM, thus improving the prognosis.
Department of Cardiac Function, People's Hospital of Zhengzhou, Zhengzhou City, Henan Province, China.
Huilei
H
Cheng
Department of Cardiac Function, People's Hospital of Zhengzhou, Zhengzhou City, Henan Province, China.
Yanqin
Y
Xi
Department of Cardiac Function, People's Hospital of Zhengzhou, Zhengzhou City, Henan Province, China.
Xianna
X
Chi
Department of Cardiac Function, People's Hospital of Zhengzhou, Zhengzhou City, Henan Province, China.
Yanxia
Y
Wu
Department of Vasculocardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, China.
Guizhi
G
Liu
Th17 cell; Treg cell; experimental autoimmune myocarditis; myocardial tissues; rat