刘婷婷;李文莲;杨嫚;朱凯;

• 1:遵义医科大学第三附属医院

摘要(Abstract)：

轮状病毒（RV）腹泻发病过程中核转录因子E2相关因子（Nrf2）/血红素加氧-1(HO-1)通路受到抑制，四神丸在溃疡性结肠炎的治疗中对Nrf2/HO-1通路具有激活作用，为了研究四神丸在RV腹泻中的治疗作用及机制，本研究观察了四神丸调控Nrf2/HO-1通路保护RV腹泻小鼠肠道损伤的作用及机制。将雄性BALB/c小鼠随机分为对照组、RV腹泻组、四神丸组、四神丸+ML385组，采用RV病毒液单次灌胃的方法建立RV腹泻模型，给予四神丸4.2g/kg灌胃、1次/d或Nrf2抑制剂ML385 30mg/kg腹腔注射、1次/d进行干预，连续3d。检测粪便中RV VP6基因拷贝数，血清中白介素（IL）-1β、IL-6、肿瘤坏死因子-α(TNF-α)、丙二醛（MDA）及总抗氧化力（T-AOC）的含量，回肠粘膜绒毛高度、隐窝深度、活性氧簇（ROS）水平、细胞凋亡率及Occludin、ZO-1、Nrf2、HO-1表达水平。结果显示，RV腹泻组粪便中RV VP6基因拷贝数、血清中IL-1β、IL-6、TNF-α、MDA含量及回肠粘膜隐窝深度、ROS水平、细胞凋亡率均高于对照组，血清T-AOC含量、回肠粘膜绒毛高度及Occludin、ZO-1、Nrf2、HO-1表达水平均低于对照组（P<0.05）；四神丸组粪便中RV VP6基因拷贝数与RV腹泻组比较无差异（P>0.05），血清中IL-1β、IL-6、TNF-α、MDA含量及回肠粘膜隐窝深度、ROS水平、细胞凋亡率均低于RV腹泻组，血清T-AOC含量、回肠粘膜绒毛高度及Occludin、ZO-1、Nrf2、HO-1表达水平均高于RV腹泻组（P<0.05）；四神丸+ML385组粪便中RV VP6基因拷贝数与四神丸组比较无差异（P>0.05），血清中IL-1β、IL-6、TNF-α、MDA含量及回肠粘膜隐窝深度、ROS水平、细胞凋亡率均高于四神丸组，血清T-AOC含量、回肠粘膜绒毛高度及Occludin、ZO-1、Nrf2、HO-1表达水平均低于四神丸组（P<0.05）。以上结果表明四神丸对RV腹泻小鼠的回肠绒毛结构及黏膜屏障具有保护作用，激活Nrf2/HO-1通路并减轻氧化应激、炎症反应及细胞凋亡是相关的分子机制。本研究的创新点以回肠绒毛结构及黏膜屏障损伤切入点观察了四神丸在RV腹泻中的治疗价值，发现四神丸通过激活Nrf2/HO-1通路减轻RV腹泻小鼠的炎症反应、氧化应激及细胞凋亡，这为今后深入认识RV腹泻的病理生理机制、发现RV腹泻新的治疗手段提供了实验依据。

关键词(KeyWords)： 轮状病毒腹泻;四神丸;肠道损伤;氧化应激;炎症反应;细胞凋亡;Nrf2/HO-1通路

Abstract:

Keywords:

基金项目(Foundation):

作者(Authors): 刘婷婷;李文莲;杨嫚;朱凯;

DOI: 10.13242/j.cnki.bingduxuebao.004250

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