Department of Gastroenterology, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China.
Department of Gastroenterology, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China.
Arch Med Res. 2019 Jan;50(1):2-9. doi: 10.1016/j.arcmed.2019.03.004. Epub 2019 Apr 4.
Previous studies have reported that nonalcoholic steatohepatitis (NASH) is relevant to intestinal mucosal barrier dysfunction.
To investigate the effects of intestinal trefoil factor 3 (TFF3) on intestinal barrier function and endotoxin/toll-like receptor 4(TLR4) expression in NASH rats.
Sixty NASH rats were divided into control, NASH and NASH-TFF3 treated group. Intestinal permeability, serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), endotoxin (ET), diamine oxidase (DAO) and liver index were examined. HE and PAS staining were performed to observe the histopathology of liver and terminal ileum. Expression of TFF3 and occludin were detected by immunohistochemical staining. mRNA and protein expression of TLR4, nuclear factor-κB (NF-κB), Mucin-2(Muc2) were detected by RT-qPCR and Western Blot. Interleukin (IL) -1β and IL-10 levels in the ileum were measured by ELISA.
In NASH group, levels of AST, ALT, ET, DAO, NAS, liver index and intestinal permeability were higher while occludin expressions were lower than control and NASH-TFF3 treated groups (p <0.05). Histopathology examination showed pathological damages of liver and ileum were alleviated in NASH-TFF3 treated group. NASH-TFF3 treated group had decreased expression levels of TLR4 and NF-κB and increased expression levels of Muc2 than NASH group. Besides, NASH group showed increased IL-1β and IL-10 levels compared with control group. NASH-TFF3 treated group showed decreased IL-1β level however increased IL-10 level compared with NASH group.
Recombinant human TFF3 (rhTFF3) can reduce the expression of TLR4, reduce intestinal permeability, alleviate liver damage and thus may play a therapeutic role in the treatment of NASH rats.
先前的研究报告指出，非酒精性脂肪性肝炎（NASH）与肠黏膜屏障功能障碍有关。
研究肠三叶因子 3（TFF3）对 NASH 大鼠肠道屏障功能和内毒素/ toll 样受体 4（TLR4）表达的影响。
将 60 只 NASH 大鼠分为对照组、NASH 组和 NASH-TFF3 治疗组。检测肠道通透性、血清天门冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、内毒素（ET）、二胺氧化酶（DAO）和肝指数。行肝和末端回肠组织 HE 和 PAS 染色观察组织病理学变化。免疫组织化学染色检测 TFF3 和闭合蛋白的表达。通过 RT-qPCR 和 Western blot 检测 TLR4、核因子-κB（NF-κB）、黏蛋白-2（Muc2）的 mRNA 和蛋白表达。通过 ELISA 检测回肠中白细胞介素（IL）-1β和 IL-10 的水平。
NASH 组 AST、ALT、ET、DAO、NAS、肝指数和肠道通透性水平均高于对照组和 NASH-TFF3 治疗组，而闭合蛋白表达水平低于对照组和 NASH-TFF3 治疗组（p<0.05）。NASH-TFF3 治疗组肝和回肠的组织病理学损伤较 NASH 组减轻。NASH-TFF3 治疗组 TLR4 和 NF-κB 的表达水平低于 NASH 组，Muc2 的表达水平高于 NASH 组。此外，NASH 组 IL-1β 和 IL-10 水平较对照组升高。NASH-TFF3 治疗组与 NASH 组相比，IL-1β 水平降低，而 IL-10 水平升高。
重组人 TFF3（rhTFF3）可降低 TLR4 表达，减少肠道通透性，减轻肝损伤，从而可能在治疗 NASH 大鼠中发挥治疗作用。
