丹参素衍生物对DSS诱导的急性结肠炎的保护机制研究
首发时间:2019-02-11
摘要:前期研究表明,一种从丹参素中提取的新型丹参素衍生物DSC(4-(2-乙酰氧基-3- ((R-3-(苄硫基)-1-甲氧基-1-氧代丙-2-基氨基)-3-氧代丙-1,2-亚苯基二乙酸酯)),在细胞水平上有显著的抗炎抗氧化能力。为了探究DSC对葡聚糖硫酸钠(DSS)诱导的急性结肠炎潜在的功效。采用2.5%(w/v)DSS混于饮用水的方法建立7天急性结肠炎模型,将30只C57BL/6J 雄性小鼠均分为正常对照组,模型组和造模同时DSC(50mg/kg)给药组。每天等量腹腔注射,并记录小鼠体重及疾病活动指数(DAI)。结束后取结肠,测定长度,采用酶联免疫法测定MPO活性和炎症因子水平及紧密连接蛋白表达,通过H&E染色法进行结肠组织病理学评估,采用蛋白免疫印迹法检测结肠NLR热蛋白结构域亚家族成员3(NLRP3)及核因子(NF)-κB信号活性,荧光染色法测定结肠组织的ROS表达。结果表明,与模型组相比,给药组体重降低缓慢,且DAI评分较低。表现出更少的炎症细胞浸润,隐窝发炎及固有层的缺失。紧密连接蛋白ZO-2,Claudin-1表达显著上调,炎症因子IL-6,IL-18,IL-1β及MPO的表达显著降低。DSC给药显著抑制了NF-κB炎症信号及NLRP3炎症小体的激活,同时减缓了ROS的聚集。
关键词: 丹参素衍生物 急性结肠炎 肠道屏障;NLRP3炎症小体 氧化应激
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DSC ameliorates DSS-induced colitis
Abstract:Previously reports have demostrated a novel compound derived from danshensu, exhibits cytoprotective activities in vitro. Here, we aimed to evaluate the effects and underlying mechanisms of DSC on dextran sodium sulfate (DSS)-induced experimental colitis. A 7-day acute colitis model was established using 2.5% (w/v) DSS in drinking water. Thirty male C57BL/6J mice were divided into normal control group, model group and model with DSC (50 mg/kg) administration group. During the experiment, intraperitoneal injection was performed at the same time every day, and the body weight and disease activity index (DAI) of the mice were recorded. After the experiment, the colon were taken, the length was determined, MPO activity, inflammatory factor levels and intestinal barrier were determined by enzyme-linked immunosorbent assay. histopathological evaluation by HE staining, detection of colonic NLR thermoprotein domain subfamily member 3 (NLRP3) and nuclear factor (NF)-κB signaling pathway by Western blotting. The level of ROS expression in colon tissue was determined. The results showed that, compared with the model group, the weight loss and DAI index was slower in DSC group.Pathological evaluation showed less inflammatory cell infiltration, crypt inflammation and loss of lamina propria.The expreesion of Intestinal tight junction protein ZO-2, Claudin-1 were incraesed,while inflammatory factors IL-6, IL-18, IL-1β and MPO expression were significantly reduced. Intraperitoneal injection of DSC significantly inhibited the activation of NF-κB signal pathway and NLRP3 inflammation , ROS accumulation was significantly reduced.
Keywords: DSC Colitis Intestinal barrier NLRP3 Inflammasome Oxidative stress
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丹参素衍生物对DSS诱导的急性结肠炎的保护机制研究
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