Tang Shi, Gao Chenlin, Long Yang, Huang Wei, Chen Jiao, Fan Fang, Jiang Chunxia, Xu Yong
Endocrinology Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; The Graduate School of Southwest Medical University, Luzhou, Sichuan 646000, China.
State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau.
Mediators Inflamm. 2017;2017:2438247. doi: 10.1155/2017/2438247. Epub 2017 Jan 15.
. Inflammation and fibrosis are the important pathophysiologic processes in diabetic nephropathy (DN). Maresin 1 is a potential anti-inflammatory lipid mediator, which has displayed powerful proresolving activities. . We determine whether maresin 1 has protective effect on mouse glomerular mesangial cells (GMCs) induced by high glucose. . We cultured GMCs stimulated by high glucose and categorized as follows: normal glucose group (5.6 mmol/L), high glucose group (30 mmol/L), mannitol group, maresin 1 intervention group (1, 10, and 100 nmol/L), maresin 1 and normal glucose group, and the N-acetylcysteine (NAC) intervention group (10 mol/L NAC). After 24 h, the expression of ROS, NLRP3, caspase-1, procaspase-1, IL-1, and pro-IL-1 was detected by western-blot, RT-PCR, and immunofluorescence. After 48 h, the expression of TGF-1 and FN was detected by RT-PCR and ELISA. . Compared with normal glucose group, the expression of ROS, NLRP3, caspase-1, IL-1, TGF-1, and FN increased in high glucose group ( < 0.05), but it decreased after the treatment of maresin 1 in different concentrations. On the contrary, the expression of procaspase-1 and pro-IL-1 protein was restrained by high glucose and enhanced by maresin 1 in a dose-dependent manner ( < 0.05). . Maresin 1 can inhibit NLRP3 inflammasome, TGF-1, and FN in GMCs; it may have protective effect on DN by mitigating the inflammation and early fibrosis.
炎症和纤维化是糖尿病肾病(DN)的重要病理生理过程。maresin 1是一种潜在的抗炎脂质介质,具有强大的促消退活性。我们确定maresin 1对高糖诱导的小鼠肾小球系膜细胞(GMCs)是否具有保护作用。我们培养了受高糖刺激的GMCs,并进行如下分组:正常葡萄糖组(5.6 mmol/L)、高糖组(30 mmol/L)、甘露醇组、maresin 1干预组(1、10和100 nmol/L)、maresin 1与正常葡萄糖组以及N-乙酰半胱氨酸(NAC)干预组(10 μmol/L NAC)。24小时后,通过蛋白质免疫印迹法、逆转录-聚合酶链反应(RT-PCR)和免疫荧光检测活性氧(ROS)、NLRP3、半胱天冬酶-1、前半胱天冬酶-1、白细胞介素-1(IL-1)和前IL-1的表达。48小时后,通过RT-PCR和酶联免疫吸附测定(ELISA)检测转化生长因子-β1(TGF-β1)和纤连蛋白(FN)的表达。与正常葡萄糖组相比,高糖组中ROS、NLRP3、半胱天冬酶-1、IL-1、TGF-β1和FN的表达增加(P<0.05),但不同浓度的maresin 1处理后其表达降低。相反,高糖抑制前半胱天冬酶-1和前IL-1蛋白的表达,而maresin 1以剂量依赖性方式增强其表达(P<0.05)。Maresin 1可抑制GMCs中的NLRP3炎性小体、TGF-β1和FN;它可能通过减轻炎症和早期纤维化对糖尿病肾病具有保护作用。