摘要
目的 研究沉默信息调节因子1(SIRT1)在复方苦参汤治疗溃疡性结肠炎中的作用。方法 采用3%葡聚糖硫酸钠(DSS)建立小鼠溃疡性结肠炎模型,随机分为对照组,模型组,复方苦参汤低、中、高剂量组(3、6、12 g/kg,灌肠),柳氮磺吡啶组(300 mg/kg,灌胃),复方苦参汤(12 g/kg,灌肠)+SIRT1抑制剂(5 mg/kg EX527,腹腔注射)组,造模当天开始连续给药7 d。计算疾病活动指数(DAI),HE染色观察结肠病理变化,免疫组化法检测结肠组织SIRT1表达,ELISA法检测结肠肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-6、IL-1β水平和髓过氧化物酶(MPO)活性,超氧化物阴离子荧光探针(DHE)和试剂盒分别检测结肠活性氧(ROS)水平和丙二醛(MDA)水平,Western blot法检测结肠组织乙酰化核因子κB(Acetyl NF-κB)、锰超氧化物歧化酶(SOD2)和过氧化氢酶(CAT)蛋白表达。结果 与模型组比较,柳氮磺吡啶组和复方苦参汤各剂量组小鼠DAI评分和结肠病理损伤均得到改善(P<0.01),SIRT1、SOD2、CAT表达升高(P<0.05,P<0.01),而Acetyl NF-κB蛋白表达、TNF-α、IL-6、IL-1β、MDA水平和ROS、MPO活性则降低(P<0.05,P<0.01)。EX527减弱了复方苦参汤对溃疡性结肠炎小鼠氧化应激和炎症反应的保护作用(P<0.05,P<0.01)。结论 复方苦参汤对小鼠溃疡性结肠炎的保护作用可能与其激活SIRT1信号通路有关。
AIM To investigate the role of silent information regulator 1(SIRT1) in the treatment of ulcerative colitis(UC) with Compound Sophorae Decoction.METHODS With the establishment of mouse UC models by 3% dextran sodium sulfate(DSS), the mice were randomly divided into the control group, the model group, low-dose, medium-dose and high-dose Compound Sophorae Decoction groups(3, 6, 12 g/kg, enema), sulfasalazine group(300 mg/kg, gavage) and Compound Sophorae Decoction(12 g/kg, enema) + SIRT1 inhibitor(5 mg/kg EX527, intraperitoneal injection) group for 7 days consecutive corresponding administration concurrent with the modeling. The mice had their disease activity index(DAI) calculated;their colon pathological changes detected by HE staining;their colon SIRT1 expression determined by immunohistochemistry;their levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1β and myeloperoxidase(MPO) activity determined by ELISA;their colon levels of reactive oxygen species(ROS) and malondialdehyde(MDA) detected respectively by superoxide anion fluorescent probe(DHE) and kit;and their colon expressions of acetylated nuclear factor κB(Acetyl NF-κB), manganese superoxide dismutase(SOD2) and catalase(CAT) detected by Western blot.RESULTS Compared with the model group, sulfasalazine group and each group dosed with Compound Sophorae Decoction were observed with improved DAI index and degree of colon tissue pathological damage(P<0.01);increased expressions of SIRT1, SOD2 and CAT(P<0.05,P<0.01);decreased expression of Acetyl NF-κB protein, levels of TNF-α, IL-6, IL-1β, MDA and the activities of ROS and MPO(P<0.05, P<0.01). EX527 attenuated the protective effects of Compound Sophorae Decoction on UC mice in terms of the oxidative stress and inflammatory response(P<0.05,P<0.01). CONCLUSION The protective effects of Compound Sophorae Decoction on UC mice may be related to the activation of SIRT1 signal pathway.
作者
林子栋
席作武
刘洪波
LIN Zi-dong;XI Zuo-wu;LIU Hong-bo(The Second College of Clinical Medicine,Henan University of Chinese Medicine,Zhengzhou 450002,China;Anorectal Department,Henan Province Hospital of Traditional Chinese Medicine,Zhengzhou 450002,China;Nanyang Medical College,Nanyang 473061,China)
出处
《中成药》
CAS
CSCD
北大核心
2023年第2期415-422,共8页
Chinese Traditional Patent Medicine
基金
河南省卫生健康委国家中医临床研究基地科研专项(2021JDZX2003)
河南中医药学科领军人才项目(豫卫中医函[2021]8号)
河南省中医药科学研究专项(2019JDZX082)。
关键词
复方苦参汤
溃疡性结肠炎
SIRT1
氧化损伤
炎症反应
Compound Sophorae Decoction
ulcerative colitis
SIRT1
oxidative damage
inflammatory response
