肝移植肝硬化大鼠肠道微生物群与先天免疫相关基因改变
Intestinal microbiota and innate immunity-related gene alteration in cirrhotic rats with liver transplantation.
作者信息
Xie Y R, Liu S L, Liu X, Luo Z B, Zhu B, Li Z F, Li L J, He Y, Jiang L, Li H, Ruan B
机构信息
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Infectious Disease Center, the First Affiliated Hospital of Medical School, Zhejiang University, Hangzhou, China.
出版信息
Transplant Proc. 2011 Dec;43(10):3973-9. doi: 10.1016/j.transproceed.2011.08.113.
BACKGROUND
The present study investigated the alteration of intestinal microbiota, innate immunity-related genes, and bacterial translocation in rats with cirrhosis and liver transplantation.
METHODS
Specific pathogen-free Sprague-Dawley rats were randomized into 4 groups: (1) normal controls (N); (2) liver cirrhosis (LC); (3) normal control groups with liver transplantation (LTN); and (4) liver cirrhosis with liver transplantation (LTC). We examined plasma endotoxin, bacterial tacslocation, denaturing gradient gel electrophoresis (DGGE) profile of intestinal mucosa-associated bacteria, abundance of key bacterial populations, and expression of innate immunity-related gene.
RESULTS
The LTC and LC group, showed higher endotoxin levels (1.08±0.73 EU/mL and 0.74±0.70 EU/mL, respectively) than the N group (0.27±0.13 EU/mL; P<.05). the incidence of bacterial translocation (BT) to liver and mesenteric lymph nodes (MLN), and the number of total bacteria were increased significantly in the LTC and LC groups compared with the N group (P<.05). The counts of Lactobacilli and Bacteroides were lower, whereas Enterobacteria were higher in the LC than the N group (P<.05). Mucins (MUC2, MUC3) and Toll-like receptors (TLR2, TLR4) messenger RNA (mRNA) expression were significantly higher in the LC and LTC groups than the N group (P<.05). The marked difference between the groups in the overall structure of the bacterial community was also generated by DGGE profiles.
CONCLUSION
Liver cirrhosis disturbs intestinal microbiota and innate immunity-related genes, which contributes to endotoxemia and bacterial translocation. These had not completely recovered in cirrhotic rats until 1 month after orthotopic liver transplantation.
背景
本研究调查了肝硬化及肝移植大鼠肠道微生物群、先天免疫相关基因及细菌易位的变化。
方法
将无特定病原体的Sprague-Dawley大鼠随机分为4组:(1)正常对照组(N);(2)肝硬化组(LC);(3)肝移植正常对照组(LTN);(4)肝硬化肝移植组(LTC)。我们检测了血浆内毒素、细菌易位、肠黏膜相关细菌的变性梯度凝胶电泳(DGGE)图谱、关键细菌种群的丰度以及先天免疫相关基因的表达。
结果
LTC组和LC组的内毒素水平(分别为1.08±0.73 EU/mL和0.74±0.70 EU/mL)高于N组(0.27±0.13 EU/mL;P<0.05)。与N组相比,LTC组和LC组向肝脏和肠系膜淋巴结(MLN)的细菌易位(BT)发生率及细菌总数显著增加(P<0.05)。LC组的乳酸杆菌和拟杆菌计数较低,而肠杆菌计数高于N组(P<0.05)。LC组和LTC组的粘蛋白(MUC2、MUC3)和Toll样受体(TLR2、TLR4)信使核糖核酸(mRNA)表达显著高于N组(P<0.05)。DGGE图谱也显示了各组细菌群落总体结构的显著差异。
结论
肝硬化扰乱肠道微生物群和先天免疫相关基因,导致内毒素血症和细菌易位。这些变化在原位肝移植后1个月内,在肝硬化大鼠中尚未完全恢复。