Shin Seung Kak, Cho Jae Hee, Kim Eui Joo, Kim Eun-Kyung, Park Dong Kyun, Kwon Kwang An, Chung Jun-Won, Kim Kyoung Oh, Kim Yoon Jae
Seung Kak Shin, Jae Hee Cho, Eui Joo Kim, Eun-Kyung Kim, Dong Kyun Park, Kwang An Kwon, Jun-Won Chung, Kyoung Oh Kim, Yoon Jae Kim, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, South Korea.
World J Gastroenterol. 2017 Jul 7;23(25):4559-4568. doi: 10.3748/wjg.v23.i25.4559.
To evaluate the anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium (DSS)-induced colitis model.
An acute colitis mouse model was induced by oral administration of 5% DSS in the drinking water for 7 d. In the treated group, rosuvastatin (0.3 mg/kg per day) was administered orally before and after DSS administration for 21 d. On day 21, mice were sacrificed and the colons were removed for macroscopic examination, histology, and Western blot analysis. In the study, IEC-6 cells were stimulated with 50 ng/mL tumor necrosis factor (TNF)-α and then treated with or without rosuvastatin (2 μmol/L). The levels of reactive oxygen species (ROS), inflammatory mediators, and apoptotic markers were measured.
In DSS-induced colitis mice, rosuvastatin treatment significantly reduced the disease activity index and histological damage score compared to untreated mice ( < 0.05). Rosuvastatin also attenuated the DSS-induced increase of 8-hydroxy-2'-deoxyguanosine and NADPH oxidase-1 expression in colon tissue. Multiplex ELISA analysis revealed that rosuvastatin treatment reduced the DSS-induced increase of serum IL-2, IL-4, IL-5, IL-6, IL-12 and IL-17, and G-CSF levels. The increased levels of cleaved caspase-3, caspase-7, and poly (ADP-ribose) polymerase in the DSS group were attenuated by rosuvastatin treatment. , rosuvastatin significantly reduced the production of ROS, inflammatory mediators and apoptotic markers in TNF-α-treated IEC-6 cells ( < 0.05).
Rosuvastatin had the antioxidant, anti-inflammatory and anti-apoptotic effects in DSS-induced colitis model. Therefore, it might be a candidate anti-inflammatory drug in patients with inflammatory bowel disease.
通过调节氧化应激，在葡聚糖硫酸钠（DSS）诱导的结肠炎模型中评估瑞舒伐他汀的抗炎和抗凋亡作用。
通过在饮用水中口服5% DSS 7天诱导急性结肠炎小鼠模型。在治疗组中，在给予DSS前后口服瑞舒伐他汀（每天0.3 mg/kg），持续21天。在第21天，处死小鼠并取出结肠进行大体检查、组织学检查和蛋白质印迹分析。在该研究中，用50 ng/mL肿瘤坏死因子（TNF）-α刺激IEC-6细胞，然后用或不用瑞舒伐他汀（2 μmol/L）处理。测量活性氧（ROS）、炎症介质和凋亡标志物的水平。
在DSS诱导的结肠炎小鼠中，与未治疗的小鼠相比，瑞舒伐他汀治疗显著降低了疾病活动指数和组织学损伤评分（P<0.05）。瑞舒伐他汀还减弱了DSS诱导的结肠组织中8-羟基-2'-脱氧鸟苷和NADPH氧化酶-1表达的增加。多重酶联免疫吸附测定分析显示，瑞舒伐他汀治疗降低了DSS诱导的血清IL-2、IL-4、IL-5、IL-6、IL-12和IL-17以及粒细胞集落刺激因子水平的升高。DSS组中裂解的半胱天冬酶-3、半胱天冬酶-7和聚（ADP-核糖）聚合酶水平的升高通过瑞舒伐他汀治疗得到减弱。此外，瑞舒伐他汀显著降低了TNF-α处理的IEC-6细胞中ROS、炎症介质和凋亡标志物的产生（P<0.05）。
瑞舒伐他汀在DSS诱导的结肠炎模型中具有抗氧化、抗炎和抗凋亡作用。因此，它可能是炎症性肠病患者的一种候选抗炎药物。
