桔梗皂苷D对大鼠溃疡性结肠炎的改善作用及对TLR4/NOD信号通路蛋白表达的影响  

Improvement of Platycodin D on Ulcerative Colitis in Rats and Effect on Protein Expression of TLR4/NOD Signaling Pathway

作　　者：金蕾 朱轶[2] JIN Lei;ZHU Yi(Dept.of Traditional Chinese Medicine,Shanghai Sixth People’s Hospital,Shanghai 201306,China;Dept.of Acupuncture,Massage and Traumatology,Shanghai Sixth People’s Hospital,Shanghai 201306,China)

机构地区：[1]上海市第六人民医院中医科,上海201306 [2]上海市第六人民医院针推伤科,上海201306

出　　处：《广州中医药大学学报》2023年第6期1462-1467,共6页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：上海浦东新区“国家中医药发展综合改革试验区”建设项目(编号:PDZY-2020-0404)。

摘　　要：【目的】探讨桔梗皂苷D对溃疡性结肠炎大鼠的治疗作用及机制。【方法】将50只大鼠随机分为5组,包括正常组,模型组,桔梗皂苷D低、中、高剂量组,每组10只。除正常组大鼠给予蒸馏水饮用外,其他组大鼠通过在饮用水中施加5%硫酸葡萄糖钠(DSS)连续7 d诱导构建溃疡性结肠炎模型。实验第2~8周,桔梗皂苷D低、中、高剂量组大鼠分别灌胃10、25、50 mg·kg^(-1)·d^(-1)桔梗皂苷D混悬液,正常组和模型组大鼠灌胃等体积蒸馏水。给药期间,观察大鼠一般情况。给药结束后,采用苏木素-伊红(HE)染色法观察结肠组织病理形态并进行组织学评分,Western Blot法检测结肠组织Toll样受体4(TLR4)/核苷酸结合寡聚化结构域(NOD)通路相关蛋白TLR4、髓样分化因子88(MyD88)和NOD样受体热蛋白结构域相关蛋白3(NLRP3)表达水平。【结果】(1)与正常组比较,模型组大鼠体质量、生存率、结肠长度和结肠质量均显著降低,疾病活动指数(DAI)评分显著升高(均P<0.01);与模型组比较,桔梗皂苷D低、中、高剂量组大鼠体质量、生存率、结肠长度和结肠质量均显著升高,DAI评分显著降低,其中,桔梗皂苷D中剂量组差异均有统计学意义(P<0.05或P<0.01)。(2)与正常组比较,模型组结肠组织病理学评分升高(P<0.001);与模型组比较,桔梗皂苷D低、中、高剂量组结肠组织病理学评分均显著降低(P<0.05或P<0.01)。(3)与正常组比较,模型组中TLR4、MyD88和NLRP3的蛋白表达水平显著升高(P<0.01);与模型组比较,桔梗皂苷D中剂量组的TLR4、MyD88和NLRP3蛋白表达水平显著降低(P<0.05)。【结论】桔梗皂苷D可改善大鼠溃疡性结肠炎,其机制与通过TLR4/NOD信号通路缓解肠道炎症有关。Objective To investigate the therapeutic effect and mechanism of platycodin D in mice with ulcerative colitis.Methods Fifty rats were randomly divided into 5 groups,including normal group,model group,and low-,medium-and high-dose of platycodin D groups,with 10 rats in each group.A model of ulcerative colitis was constructed by administering 5%dextran sulfate sodium(DSS)in the drinking water for 7 days,except for the normal group,which was given distilled water to drink.From weeks 2 to 8,rats in the low-,medium-and highdose groups were gavaged with 10,25 and 50 mg·kg^(-1)·d^(-1)of platycodin D,respectively,while rats in the normal and model groups were gavaged with equal volume of distilled water.During the administration,the general condition of the rats was observed.After the administration,the histopathological morphology of the colon was observed and histologically scored by hematoxylin-eosin staining,and the colonic Toll-like receptor 4(TLR4)and nucleotide-binding oligomerization structural domain(NOD)pathway-related proteins TLR4,myeloid differentiation factor 88(MyD88)and NOD-like receptor heat protein domain-associated protein 3(NLRP3)were detected by Western Blot.Results(1)Compared with the normal group,body mass,survival rate,colon length and colon mass were significantly decreased and disease activity index(DAI)score was significantly increased in the model group(all P<0.01);compared with the model group,body mass,survival rate,colon length and colon mass were significantly increased and DAI score was significantly decreased in the low-,medium-and highdose groups of platycodin D.Among them,the difference in the medium-dose group of platycodin D was statistically significan(t P<0.05 or P<0.01).(2)Compared with the normal group,the colon histopathology score was increased in the model group(P<0.001);compared with the model group,the colon histopathology score was significantly decreased in the low-,medium-and high-dose groups of platycodin D(P<0.05 or P<0.01).(3)The protein expression levels of TLR4,MyD

关 键 词：桔梗皂苷D 溃疡性结肠炎 Toll样受体4(TLR4)/核苷酸结合寡聚化结构域(NOD)信号通路 NOD样受体热蛋白结构域相关蛋白3(NLRP3) 炎症 大鼠 

分 类 号：R285.5[医药卫生—中药学]