Lou Xu-dan, Wang Hai-dong, Xia Shi-jin, Skog Sven, Sun Jiao
Endocrinology Department, Huadong Hospital, Fudan University, NO. 221 West of Yan'an Road, Shanghai, 200040, China.
Arch Immunol Ther Exp (Warsz). 2014 Aug;62(4):329-40. doi: 10.1007/s00005-014-0271-4. Epub 2014 Feb 5.
This paper studies the expression of proinflammatory cytokines such as IL-1β, IL-6, TNF-α, and IFN-γ 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-1β, IL-6, TNF-α, and IFN-γ 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-1β, IL-6, TNF-α, and IFN-γ, 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.
本文研究了糖尿病大鼠主动脉中促炎细胞因子如白细胞介素 -1β（IL-1β）、白细胞介素 -6（IL-6）、肿瘤坏死因子 -α（TNF-α）和干扰素 -γ（IFN-γ）以及抗炎细胞因子如白细胞介素 -10（IL-10）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。实验在分为四组的大鼠上进行：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组用白藜芦醇治疗。3个多月后，取出大鼠主动脉，通过免疫组织化学、蛋白质印迹法、实时聚合酶链反应（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在糖尿病大鼠的动脉内膜中发现。DM组中IL-1β、IL-6、TNF-α和IFN-γ的蛋白质和mRNA表达水平显著高于NC组（p < 0.05），而在白藜芦醇治疗组（NB和DB）中，这些水平相对低于相应组。相对于NC组，DM组在IL-1β、IL-6、TNF-α和IFN-γ的特定胞嘧啶 - 磷酸 - 鸟嘌呤位点的DNA甲基化水平降低（p < 0.01），白藜芦醇可使其升高。相反，IL-10在高糖作用下显著甲基化并表达降低，白藜芦醇可逆转这种作用。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，因此可能对高血糖状态下的主动脉具有保护作用。因此，DNA甲基化这种表观遗传基因沉默信号可能是这两种现象的原因。
