Effects of Resveratrol on the Expression and DNA Methylation of Cytokine Genes in Diabetic Rat Aortas
Effects of Resveratrol on the Expression and DNA Methylation of Cytokine Genes in Diabetic Rat Aortas
复制标题
白藜芦醇对糖尿病大鼠主动脉细胞因子基因表达及DNA甲基化的影响
DOI：
10.1007/s00005-014-0271-4
复制
发表时间：
2014-08-01
影响因子：
3.2
通讯作者：
Sun, Jiao
中科院分区：
文献类型：
--
作者：
Lou, Xu-dan;Wang, Hai-dong;Sun, Jiao
本文研究了促炎细胞因子如IL-1 β、IL-6、TNF-α和IFN-γ和抗炎细胞因子如IL-10在糖尿病大鼠牙周组织中的表达，白藜芦醇对这些细胞因子的影响，以及潜在的表观遗传机制。实验分为正常组（NC）、正常干预组（NB）、糖尿病组（DM）和糖尿病干预组（DB）。NB组和DB组给予白藜芦醇治疗。超过3个月后，取出大鼠的睾丸，并通过免疫组织化学、Western印迹、实时PCR和甲基化特异性PCR分析细胞因子。这些细胞因子的组织学定位主要发现在糖尿病大鼠动脉内膜。DM组IL-1 β、IL-6、TNF-α和IFN-γ的蛋白和mRNA表达水平显著高于NC组（p < 0.05），而白藜芦醇治疗组（NB和DB）的水平相对低于相应组。与NC组相比，DM组IL-1 β、IL-6、TNF-α和IFN-γ的特异性胞嘧啶磷酸鸟苷位点的DNA甲基化水平降低（p < 0.01），白藜芦醇可增加这些水平。与此相反，IL-10显着甲基化，并显示在响应于高葡萄糖的表达下降，白藜芦醇逆转了这种作用。这些结果表明，炎症反应参与糖尿病大血管病变。白藜芦醇抑制促炎细胞因子的表达，因此可能对高血糖时的主动脉具有保护作用。因此，DNA甲基化，表观遗传基因沉默信号，可能是负责这两种现象。
This paper studies the expression of proinflammatory cytokines such as IL-1 beta, IL-6, TNF-alpha, and IFN-gamma and anti-inflammatory cytokines such as IL-10 in diabetic rat aortas, the effects of resveratrol on these cytokines, and the potential epigenetic mechanisms involved. The experiment was performed on rats divided into four groups: normal group (NC), normal interventional group (NB), diabetic group (DM), and diabetic interventional group (DB). The NB and DB groups were treated with resveratrol. After more than 3 months, the rats' aortas were removed and analyzed for cytokines by using immunohistochemistry, Western blotting, real-time PCR, and methylation-specific PCR. Histological localization of these cytokines was mainly found in the arterial intima of diabetic rats. The protein and mRNA expression levels of IL-1 beta, IL-6, TNF-alpha, and IFN-gamma were significantly higher in the DM group than in the NC group (p < 0.05), whereas in the resveratrol-treated groups (NB and DB), the levels were relatively lower than those in the corresponding groups. The DM group showed reduced levels of DNA methylation at the specific cytosine phosphate guanosine sites of IL-1 beta, IL-6, TNF-alpha, and IFN-gamma, relative to those in the NC group (p < 0.01), and these levels were increased by resveratrol. In contrast, IL-10 was dramatically methylated and showed decreased expression in response to high glucose, and resveratrol reversed this effect. These results demonstrate that the inflammatory response is involved in diabetic macroangiopathy. Resveratrol inhibits the expression of proinflammatory cytokines and thus may have a protective effect on the aorta in hyperglycemia. Thus, DNA methylation, an epigenetic gene silencing signal, may be responsible for these two phenomena.