Department of gastroenterology and hepatology, West China hospital, Sichuan university, Guoxue Lane 37(#), 610041 Chengdu, China.
Department of gastroenterology and hepatology, Guiyang medical university, 550004 Guiyang, Guizhou province, China.
Clin Res Hepatol Gastroenterol. 2016 Nov;40(5):575-583. doi: 10.1016/j.clinre.2016.02.008. Epub 2016 Apr 6.
Bacterial translocation (BT) plays a vital role in the development of liver cirrhosis (LC); however, little is known regarding the role of gut innate immunity in cirrhosis.
To observe the influence of BT on multiple vital organs in LC and changes in the gut toll-like receptor-4 and nod-like receptor family pyrin domain containing-3 innate pathways in liver cirrhosis rats with bacterial translocation.
Wistar rats were divided into control and liver cirrhosis with and without bacterial translocation groups. Functional analysis was conducted using peripheral serum. Hematoxylin-eosin staining was performed to evaluate morphological changes in vital organs. Immunohistochemistry was performed to identify the distribution of toll-like receptor-4, nuclear factor-κ-gene binding-p65, nod-like receptor family pyrin domain containing-3, and its adaptor molecule Asc in the ileum. An enzyme-linked immunosorbent assay was conducted to measure tumor necrosis factor-α, interleukin-1β and interleukin-18 levels.
A significant decrease in the serum albumin level and an increase in the serum ammonia level were detected in the BT-positive rats compared with the BT-negative rats. Pathological injuries of the intestines and livers of the BT-positive rats were greatly increased compared with the BT-negative rats. The cirrhotic rats with bacterial translocation exhibited increased expression of toll-like receptor-4, nuclear factor-κ-gene binding-p65, nod-like receptor family pyrin domain containing-3, Asc and tumor necrosis factor-α in the intestines compared with the negative group. There were no significant differences of interleukin-1β and interleukin-18 in the intestines between these two groups.
Excessive activation of nuclear factor-κ-gene binding-p65/tumor necrosis factor-α and impaired activation of nod-like receptor family pyrin domain containing-3/Asc/interleukin-1β, interleukin-18 in the intestinal mucosa were observed in the cirrhotic rats with BT. Regulation of innate immunity in the intestinal mucosa may represent a novel strategy for the prevention and treatment of LC and its complications.
细菌易位（BT）在肝硬化（LC）的发展中起着至关重要的作用；然而，对于肝硬化中肠道固有免疫的作用知之甚少。
观察 BT 对 LC 多种重要器官的影响，并观察肝硬化大鼠 BT 时肠道 toll 样受体-4 和核苷酸结合寡聚化结构域样受体家族富含亮氨酸重复序列 3 固有途径的变化。
将 Wistar 大鼠分为对照组和肝硬化伴和不伴 BT 组。采用外周血清进行功能分析。苏木精-伊红染色评估重要器官的形态变化。免疫组化鉴定 TLR-4、核因子-κB 基因结合-p65、核苷酸结合寡聚化结构域样受体家族富含亮氨酸重复序列 3 及其衔接子分子 Asc 在回肠中的分布。酶联免疫吸附试验检测肿瘤坏死因子-α、白细胞介素-1β 和白细胞介素-18 水平。
与 BT 阴性大鼠相比，BT 阳性大鼠血清白蛋白水平显著降低，血清氨水平升高。BT 阳性大鼠的肠道和肝脏病理损伤明显高于 BT 阴性大鼠。与阴性组相比，伴有 BT 的肝硬化大鼠肠道 TLR-4、核因子-κB 基因结合-p65、核苷酸结合寡聚化结构域样受体家族富含亮氨酸重复序列 3、Asc 和肿瘤坏死因子-α表达增加。两组肠道白细胞介素-1β 和白细胞介素-18 无明显差异。
伴有 BT 的肝硬化大鼠肠黏膜核因子-κB 基因结合-p65/肿瘤坏死因子-α过度激活，核苷酸结合寡聚化结构域样受体家族富含亮氨酸重复序列 3/Asc/白细胞介素-1β、白细胞介素-18 激活受损。调节肠黏膜固有免疫可能成为预防和治疗 LC 及其并发症的新策略。
