摘要
目的 探究肠道菌群对2,4,6-三硝基苯磺酸(TNBS)诱导的肠纤维化大鼠模型的治疗作用及潜在机制。方法 将24只SD大鼠随机分为正常对照组、模型组、盐酸林可霉素组(85 mg/kg)和益生菌组(850 mg/kg),除正常对照组和模型组给予等体积生理盐水外,其余组给予相应药物灌胃,每日1次,连续5 d,次日除正常对照组外均采用TNBS诱导大鼠肠纤维化模型,再连续给予相应药物7 d。实验过程中观察大鼠一般行为表现,实验结束后收集结肠标本,进行组织学评分,并采用HE染色和Masson染色观察大鼠结肠组织损伤和纤维化程度,免疫组化检测E-cadherin、α-SMA、TGF-β1等蛋白表达,Western Blot检测TL1A、DR3的蛋白表达情况。结果 与正常对照组相比,模型组大鼠结肠受损,胶原纤维表达增加,提示肠纤维模型成功。盐酸林可霉素组可进一步加重结肠损伤和胶原纤维表达,经益生菌治疗结肠损伤和纤维化均有缓解。与模型组相比,盐酸林可霉素组大鼠TL1A/DR3蛋白表达水平升高(P<0.05),E-cadherin蛋白表达水平降低(P<0.05),α-SMA、TGF-β1蛋白表达水平升高(P<0.05),而益生菌组能够显著降低TL1A/DR3、α-SMA、TGF-β1蛋白表达水平,升高E-cadherin蛋白表达水平。结论 菌群紊乱通过激活TL1A/DR3信号调控结肠组织EMT过程促进纤维化发生,而采取益生菌干预能够缓解结肠纤维化发生。
Objective To explore the therapeutic effects and potential activity mechanisms of intestinal flora on a 2,4,6⁃trinitrobenzenesulfonic acid(TNBS)⁃induced intestinal fibrosis rat model.Methods 24 SD rats were randomly divided into normal control,model,lincomycin hydrochloride(85 mg/kg),and probiotic(850 mg/kg)groups.Except for the normal control and model groups,which were given equal volumes of normal saline,the groups were given corresponding drugs by gavage,once a day,for five consecutive days.The next day,TNBS was used to induce the rat intestinal fibrosis model in all groups except for the normal control group.The corresponding drugs were then given for 7 d.During the experiment,the general behavior of the rats was observed.After the experiment,colonic specimens were collected for histological scoring.HE and Masson staining were used to observe the degree of colon tissue damage and fibrosis.The immunohistochemical detection of E⁃cadherin,α⁃SMA,TGF⁃β1,and other proteins and the Western Blot detection of TL1A and DR3 proteins were carried out.Results Compared with the normal control group,the model group rats’colons were damaged,and the number of collagen fibers increased,indicating that the intestinal fiber model was successful.Lincomycin hydrochloride further aggravated colonic injury and collagen fiber expression,and colonic injury and fibrosis were alleviated by probiotic treatment.Compared with the model group,the lincomycin hydrochloride group had increased expression of TL1A/DR3 protein(P<0.05)and decreased expression of E⁃cadherin,α⁃SMA,and TGF⁃β1 proteins(P<0.05).However,the probiotics group had significantly reduced protein expression levels of TL1A/DR3,α⁃SMA,and TGF⁃β1,and increased levels of E⁃cadherin.Conclusions Microflora disorder promotes fibrosis by activating TL1A/DR3 signaling to regulate epithelial mesenchymal transformation in colon tissue,and probiotic intervention can alleviate colonic fibrosis.
作者
赵慧巧
张玉玲
张永鹏
靳国印
贺伟
罗飞
卢年华
ZHAO Huiqiao;ZHANG Yuling;ZHANG Yongpeng;JIN Guoyin;HE Wei;LUO Fei;LU Nianhua(College of Traditional Chinese Medicine,Hebei North University,Zhangjiakou 075132,China)
出处
《中国实验动物学报》
CAS
CSCD
北大核心
2023年第2期225-231,共7页
Acta Laboratorium Animalis Scientia Sinica
基金
河北省自然科学基金(H2020405010,H2020405027)
河北省高等学校科学技术研究项目(QN2020118)
校级自然科学研究计划项目(XJ2021029)。
关键词
大鼠肠纤维化
肠道菌群
2
4
6-三硝基苯磺酸
盐酸林可霉素
益生菌
TL1A/DR3
上皮间质转化
intestinal fibrosis in rats
intestinal flora
2,4,6⁃trinitrobenzene sulfonic acid
lincomycin hydrochloride
probiotics
TL1A/DR3
epithelial mesenchymal transformation
