Fenofibrate treatment of rats with experimental autoimmune myocarditis by alleviating Treg/Th17 disorder.
Fenofibrate treatment of rats with experimental autoimmune myocarditis by alleviating Treg/Th17 disorder.
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DOI：
10.5114/ceji.2016.58817
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Liu G
中科院分区：
文献类型：
--
作者：
Cheng H;Xi Y;Chi X;Wu Y;Liu G
探讨非诺贝特对实验性自身免疫性心肌炎（EAM）大鼠的治疗作用及其免疫学机制。 将24只大鼠随机分为3组：EAM组、非诺贝特组和对照组。EAM组和非诺贝特组皮下注射纯化的猪心肌肌球蛋白，对照组注射等量生理盐水。非诺贝特组灌胃非诺贝特100 mg/kg/d，其余各组灌胃等量生理盐水，共17 d。采用HE染色和qRT-PCR方法检测心衰大鼠心肌组织中细胞因子mRNA的表达水平，Western-blot方法检测NK-κB蛋白的表达。制备健康大鼠脾组织用于脾细胞悬液。随后，与体内试验类似地施用脾细胞以检测细胞因子mRNA水平。与对照组相比，EAM组大鼠心脏重量较其他各组重（p < 0.05），心肌组织有严重的炎性细胞浸润。EAM组/诱导组Th 17细胞相关细胞因子mRNA水平明显高于其他各组（p < 0.05），EAM组/诱导组FOX-p3 mRNA水平低于其他各组，非诺贝特组IL-10和FOX-p3 mRNA水平高于EAM组/诱导组（p < 0.05）。非诺贝特可明显抑制EAM大鼠NF-κB蛋白的上调（p < 0.05）。非诺贝特通过抑制Th 17细胞的发育和促进Tcl 4的分化，减轻了EAM大鼠Treg/Th 17紊乱，抑制炎症反应，从而改善预后。
To investigate the curative effect of fenofibrate on rats with experimental autoimmune myocarditis (EAM) and its immunological mechanism. 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. 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). 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.