基于“肠道菌群调控β-防御素2”探究败酱草对IBD肠纤维化大鼠的作用机制  

Investigation of the Mechanism of Patrinia Scabiosifolia on Intestinal Fibrosis in Rats with IBD Based on"Intestinal Flora Regulation of β-Defensin 2"

作　　者：赵慧巧 卢年华 苏雅迪 靳展洪叶 付羽佳 李仲平[1] ZHAO Hui-qiao;LU Nian-hua;SU Ya-di;JIN Zhan-hong-ye;FU Yu-jia;LI Zhong-ping(College of Traditional Chinese Medicine,Hebei North University,Zhangjiakou,075000,China;College of Basic Medicine,Hebei North College,Zhangjiakou,075000,China)

机构地区：[1]河北北方学院中医学院,张家口075000 [2]河北北方学院基础医学院,张家口075000

出　　处：《神经药理学报》2023年第1期8-15,29,共9页Acta Neuropharmacologica

基　　金：河北省自然科学基金项目(No.H2020405010,No.H2020405027);河北省高等学校科学技术研究项目(No.QN2020118);校级自然科学研究计划项目(No.XJ2021029)。

摘　　要：目的:探究败酱草提取物通过肠道菌群变化调控β-防御素2对炎症性肠病(inflammatory bowel disease, IBD)肠纤维化的治疗作用及可能机制。方法:选取36只雄性SD大鼠随机分为6组,分别为正常对照组(Normal)、模型组(Model)、柳氮磺胺吡啶阳性对照组(SASP)、败酱草高(PS-H,3.2 g·kg-1)、中(PS-M,2.2 g·kg-1)、低剂量组(PS-L,1.1 g·kg-1),除Normal组给予等体积生理盐水灌肠外,其他各组大鼠均给予2,4,6-三硝基苯磺酸(2,4,6-trinitrobenzene sulfonic acid, TNBS)的50%乙醇溶液灌肠以诱导炎症性肠病肠纤维化发生。造模后次日起连续灌胃给药7 d, 1次·d-1,Normal组和Model组给予等体积生理盐水。观察大鼠一般行为情况;革兰氏染色观察肠道粪便菌群的变化;HE染色检测结肠组织病理学改变;Masson染色观察结肠组织纤维化情况;免疫组化检测结肠组织α-平滑肌肌动蛋白(α-smooth muscle actin, α-SMA)、转化生长因子-β(transforming growth factor β,TGF-β)蛋白表达,ELISA法检测结肠组织中β-防御素2、白细胞介素-13(interleukin-13)的表达。结果:与Normal组相比,Model组大鼠结肠病理损伤严重,胶原纤维蓝染增多,提示肠纤维化模型成功。与Model组相比,PS给药组能显著改善IBD肠纤维化大鼠的病理损伤及纤维化程度,下调α-SMA,TGF-β蛋白的异常高表达(P<0.05),降低β-防御素2的表达水平(P<0.05),升高IL-13表达水平(P<0.05),改善肠道菌群紊乱现象。结论:败酱草可能通过调节肠道菌群降低β-防御素2表达进而缓解IBD肠纤维化的疾病进程。Objective:To investigatetheeffect and possiblemechanismof Patrinia scabiosifolia extract on intestinal fibrosis in inflammatory bowel disease(IBD)through intestinal flora regulation ofβ-defensin 2.Methods:Thirty-six male SD rats were selected and randomly divided into six groups:normal control group(Normal),model group(Model),salazosulfapyridine positive control group(SASP),Patrinia scabiosifolia(PS)high(3.2 g·kg'),medium(2.2 g.kg'),and low dose group(1.1 g·kg'),respectively.Except for the normal control group,which was given an equal volume of saline enema,all other groups of rats were given 50%ethanol enema with 2,4,6-trinitrobenzene sulfonic acid(TNBS)to induce the development of intestinal fibrosis in inflammatory bowel disease.The rats were administered by gavage for 7 days continuously from the second day after modeling,and equal volumes of saline were given to the normal control and model groups once daily.The general behavior of the rats was observed.Gram staining was used to detect changes in intestinal fecal flora.HE staining was used to detect histopathological changes in colonic tissue.masson staining was used to observe fibrosis in colonic tissue.Immunohistochemistry was used to detectα-SMA and TGF-βprotein expression in colon tissue.ELISA was used to detectβ-defensin 2 and IL-13 expression in colon tissue.Results:Compared with the normal control group,the model group rats showed severe colonic pathological damage and increased blue staining of collagen fibers,suggesting a successful intestinal fibrosis model.Compared with the model group,the PS group administration group could significantly improve the pathological injury and fibrosis degree of IBD intestinal fibrosis rats,down-regulate the abnormally high expression ofα-SMA,TGF-βprotein(P<0.05),reduce the expression level ofβ-defensin 2,elevate IL-13 expression levels(P<0.05),and improve the intestinal flora disorder phenomenon.Conclusion:Patrinia scabiosifolia may alleviate the disease process of intestinal fibrosis in IBD by reducingβ-d

关 键 词：败酱草 炎症性肠病 肠纤维化 Β-防御素2 肠道菌群 

分 类 号：R965[医药卫生—药理学]