Li Yong-Tao, Yu Cheng-Bo, Yan Dong, Huang Jian-Rong, Li Lan-Juan
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Hepatobiliary Pancreat Dis Int. 2016 Aug;15(4):399-405. doi: 10.1016/s1499-3872(16)60113-3.
Acute liver injury is a common clinical disorder associated with intestinal barrier injury and disturbance of intestinal microbiota. Probiotic supplementation has been reported to reduce liver injury; however, it is unclear whether enteropathogen infection exacerbates liver injury. The purpose of this study was to address this unanswered question using a rat model.
Oral supplementation with Salmonella enterica serovar enteritidis (S. enteritidis) was given to rats for 7 days. Different degrees of acute liver injury were then induced by intraperitoneal injection of D-galactosamine. The presence and extent of liver injury was assayed by measuring the concentrations of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin. Histology was used to observe liver tissue damage. Additionally, we measured the changes in plasma endotoxin, serum cytokines and bacterial translocation to clarify the mechanisms underlying intestinal microbiota associated liver injury.
The levels of liver damage and endotoxin were significantly increased in the Salmonella infected rats with severe liver injury compared with the no infection rats with severe liver injury (P<0.01); The peyer's patch CD3+ T cell counts were increased significantly when the Salmonella infection with severe injury group was compared with the normal group (P<0.05). S. enteritidis pretreatment enhanced intestinal barrier impairment and bacterial translocation.
Oral S. enteritidis administration exacerbates acute liver injury, especially when injury was severe. Major factors of the exacerbation include inflammatory and oxidative stress injuries induced by the translocated bacteria and associated endotoxins, as well as over-activation of the immune system in the intestine and liver.
急性肝损伤是一种常见的临床病症，与肠道屏障损伤及肠道微生物群紊乱有关。据报道，补充益生菌可减轻肝损伤；然而，肠道病原体感染是否会加重肝损伤尚不清楚。本研究旨在使用大鼠模型解决这一未解答的问题。
给大鼠口服肠炎沙门氏菌肠炎血清型（肠炎沙门氏菌）7天。然后通过腹腔注射D-半乳糖胺诱导不同程度的急性肝损伤。通过测量血清丙氨酸转氨酶、天冬氨酸转氨酶和总胆红素的浓度来测定肝损伤的存在及程度。采用组织学方法观察肝组织损伤情况。此外，我们测量了血浆内毒素、血清细胞因子的变化以及细菌移位情况，以阐明肠道微生物群相关性肝损伤的潜在机制。
与未感染严重肝损伤大鼠相比，感染沙门氏菌的严重肝损伤大鼠的肝损伤水平和内毒素水平显著升高（P<0.01）；与正常组相比，严重损伤沙门氏菌感染组的派伊尔氏结CD3+T细胞计数显著增加（P<0.05）。肠炎沙门氏菌预处理会加重肠道屏障损伤和细菌移位。
口服肠炎沙门氏菌会加重急性肝损伤，尤其是在损伤严重时。加重的主要因素包括移位细菌和相关内毒素诱导的炎症和氧化应激损伤，以及肠道和肝脏免疫系统的过度激活。
