Protective effects of SIRT1 in patients with proliferative diabetic retinopathy via the inhibition of IL-17 expression
Protective effects of SIRT1 in patients with proliferative diabetic retinopathy via the inhibition of IL-17 expression
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DOI：
10.3892/etm.2015.2877
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发表时间：
2016-01-01
影响因子：
2.7
通讯作者：
Liu, Xin
中科院分区：
文献类型：
--
作者：
Liu, Shulin;Lin, Yu;Liu, Xin
糖尿病视网膜病变（DR）是糖尿病的慢性微血管并发症，可能导致视力丧失。DR的发病机制复杂，辅助性T细胞（Th）17和白细胞介素（IL）17的表达水平升高与DR的发生和发展有关。SIRT 1是一种依赖于烟酰胺腺嘌呤二核苷酸（+）的组蛋白脱乙酰酶，在DR患者中表达下调。17.在本研究中，招募了19例增殖性糖尿病视网膜病变（PDR）患者和20例非糖尿病对照特发性黄斑前膜，并使用免疫组织化学分析了切除标本的SIRT 1表达水平。采用酶联免疫吸附试验（ELISA）检测PDR患者和对照组血清中IL-17的表达水平。此外，SIRT 1 mRNA和蛋白质表达水平在外周血单核细胞（PBMC）从两组进行了分析后，与或不与SIRT 1激活剂，白藜芦醇培养。采用ELISA法检测PBMC培养上清中IL-17的表达水平，结果表明PDR患者血清中IL-17的表达水平较对照组明显升高。此外，分别在从PDR患者采集的纤维血管膜和PBMC中检测到SIRT 1和IL-17的表达水平增加。值得注意的是，在PDR患者的PBMC中SIRT 1 mRNA和蛋白表达水平降低，并且在SIRT 1激活后IL-17的产生受到抑制。本研究结果表明，IL-17和SIRT 1表达水平的失衡可能有助于DR的发病机制，SIRT 1可能通过抑制IL-17的产生而在PDR中起保护作用。
Diabetic retinopathy (DR) is a chronic microvascular complication of diabetes that may lead to loss of vision. The pathogenesis of DR is complex and elevated expression levels of T helper (Th)17 cells and interleukin (IL)-17 have been suggested to be associated with the development and progression of DR. Sirtuin 1 (SIRT1) is a nicotinamide-adenine dinucleotide(+) -dependent histone deacetylase that is downregulated in patients with DR. Previous studies have demonstrated that SIRT1 is capable of inhibiting the production of IL-17. In the present study, 19 patients with proliferative diabetic retinopathy (PDR) and 20 non-diabetic controls with idiopathic macular epiretinal membranes were recruited and the SIRT1 expression levels of excised specimens were analyzed using immunohistochemistry. IL-17 expression levels in the sera from patients with PDR and controls were determined by enzyme-linked immunosorbent assay (ELISA). Furthermore, SIRT1 mRNA and protein expression levels in peripheral blood mononuclear cells (PBMCs) from the two groups were analyzed following culture with or without a SIRT1 activator, resveratrol. IL-17 expression levels in the supernatants of PBMCs were determined using ELISA and the results demonstrated that IL-17 expression levels were increased in the sera of patients with PDR, as compared with the controls. Furthermore, increased expression levels of SIRT1 and IL-17 were detected in fibrovascular membranes and PBMCs harvested from patients with PDR, respectively. Notably, SIRT1 mRNA and protein expression levels were decreased in the PBMCs of patients with PDR and IL-17 production was inhibited following SIRT1 activation. The results of the present study indicated that imbalanced IL-17 and SIRT1 expression levels may contribute to the pathogenesis of DR, and SIRT1 may have a protective role in PDR by inhibiting the production of IL-17.