Division of Gastroenterology, Department of Medicine, University of California, San Diego, School of Medicine, 9500 Gilman Drive, MC no. 0702, Leichtag Biomedical Research Building, Room no. 118B, La Jolla, CA 92093-0702, USA.
J Physiol. 2012 Feb 1;590(3):447-58. doi: 10.1113/jphysiol.2011.219691. Epub 2011 Nov 28.
Liver fibrosis occurs as a wound-healing scar response following chronic liver inflammation including alcoholic liver disease, non-alcoholic steatohepatitis, viral hepatitis, cholestatic liver disease and autoimmune liver diseases. The liver has a unique vascular system within the gastrointestinal tract, as the majority of the liver's blood supply comes from the intestine through the portal vein. When the intestinal barrier function is disrupted, an increase in intestinal permeability leads to the translocation of intestine-derived bacterial products such as lipopolysaccharide (LPS) and unmethylated CpG containing DNA to the liver via the portal vein. These gut-derived bacterial products stimulate innate immune receptors, namely Toll-like receptors (TLRs), in the liver. TLRs are expressed on Kupffer cells, endothelial cells, dendritic cells, biliary epithelial cells, hepatic stellate cells, and hepatocytes. TLRs activate these cells to contribute to acute and chronic liver diseases. This review summarizes recent studies investigating the role of TLRs, intestinal microbiota and bacterial translocation in liver fibrosis, alcoholic liver disease and non-alcoholic steatohepatitis.
肝纤维化是一种慢性肝炎症（包括酒精性肝病、非酒精性脂肪性肝炎、病毒性肝炎、胆汁淤积性肝病和自身免疫性肝病）后的伤口愈合疤痕反应。肝脏在胃肠道内具有独特的血管系统，因为肝脏的大部分血液供应来自肠道，通过门静脉进入肝脏。当肠道屏障功能被破坏时，肠道通透性增加会导致肠道来源的细菌产物（如脂多糖[LPS]和含有未甲基化 CpG 的 DNA）通过门静脉转移到肝脏。这些肠道来源的细菌产物刺激肝脏中的先天免疫受体，即 Toll 样受体（TLRs）。TLRs 表达于枯否细胞、内皮细胞、树突状细胞、胆管上皮细胞、肝星状细胞和肝细胞。TLRs 激活这些细胞，导致急性和慢性肝病的发生。本文综述了最近关于 TLRs、肠道微生物群和细菌易位在肝纤维化、酒精性肝病和非酒精性脂肪性肝炎中的作用的研究。
