Hepatic dysfunction induced by intestinal dysbacteriosis mainly manifests as immunologic abnormity in mice
Hepatic dysfunction induced by intestinal dysbacteriosis mainly manifests as immunologic abnormity in mice
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小鼠肠道菌群失调引起的肝功能障碍主要表现为免疫异常。
DOI：
10.1093/femspd/ftaa041
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发表时间：
2020-08-01
影响因子：
3.3
通讯作者：
Zhou, Lian
中科院分区：
文献类型：
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作者：
Luo, Xia;Xu, Bo;Zhou, Lian
目前，肝脏免疫系统和肠道菌群发生的改变在肝损伤中的潜在作用尚不清楚。本研究旨在探讨头孢曲松引起的肠道微生物屏障损伤对肝脏免疫的影响。我们通过给药头孢曲松建立BALB/c小鼠模型。采用16S rDNA观察肠道微生物屏障损伤情况，H&E或透射电镜观察肠道和肝脏病理变化。流式细胞术检测免疫细胞活化情况；采用鲎试验或ELISA法检测LPS、ALT、AST、IL-6、TNF-α的表达。与对照组相比，头孢曲松组肠道微生物明显减少。盲肠内容物重量增加，肠壁变薄，小肠和盲肠绒毛受损。LPS表达量和肝淋巴细胞比例均显著升高。H&E结果显示肝脏结构发生了病理改变。血清ALT、AST、IL-6、TNF-α含量升高。综上所述，我们的研究表明，头孢曲松引起的肠道微生物屏障的破坏，促进了免疫细胞的激活和炎症细胞因子的释放，从而可能导致肝脏的慢性炎症。
Currently, the potential role of the alterations occurring in the liver immune system and intestinal flora in liver injury remains unknown. Our study aimed to explore the impacts of intestinal microbial barrier damage induced by ceftriaxone on liver immunity. We developed the BALB/c mice model by administering ceftriaxone. The intestinal microbial barrier damage was observed by 16S rDNA, and the pathological changes of intestines and livers were detected by H&E or transmission electron microscope. The activation of immunocytes were tested by Flow Cytometry; the expression of LPS, ALT, AST, IL-6 and TNF-α were detected by Limulus Test or ELISA. Compared to the control, the intestinal microbes significantly decreased in ceftriaxone group. Additionally, the weight of cecum contents increased, the intestinal wall became thinner, and the villus in the small intestine and cecum were damaged. The expression of LPS and the ratio of liver lymphocytes were significantly increased. H&E results indicated the structures of liver arose the pathologic changes. Meanwhile, the content of serum ALT, AST, IL-6 and TNF-α increased. Collectively, our study indicates that the damages of gut microbial barrier induced by ceftriaxone prompted activation of immunocytes and release of inflammatory cytokines, which may lead to chronic inflammation in liver.