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肠道微生物群改变对肝移植后急性排斥反应大鼠肝损伤的影响。

Effect of intestinal microbiota alteration on hepatic damage in rats with acute rejection after liver transplantation.

作者信息

Xie Yirui, Chen Huazhong, Zhu Biao, Qin Nan, Chen Yunbo, Li Zhengfeng, Deng Min, Jiang Haiyin, Xu Xiangfei, Yang Jiezuan, Ruan Bing, Li Lanjuan

机构信息

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.

出版信息

Microb Ecol. 2014 Nov;68(4):871-80. doi: 10.1007/s00248-014-0452-z. Epub 2014 Jul 9.

Abstract

The previous studies all focus on the effect of probiotics and antibiotics on infection after liver transplantation. Here, we focus on the effect of gut microbiota alteration caused by probiotics and antibiotics on hepatic damage after allograft liver transplantation. Brown-Norway rats received saline, probiotics, or antibiotics via daily gavage for 3 weeks. Orthotopic liver transplantation (OLT) was carried out after 1 week of gavage. Alteration of the intestinal microbiota, liver function and histopathology, serum and liver cytokines, and T cells in peripheral blood and Peyer's patch were evaluated. Distinct segregation of fecal bacterial diversity was observed in the probiotic group and antibiotic group when compared with the allograft group. As for diversity of intestinal mucosal microbiota and pathology of intestine at 2 weeks after OLT, antibiotics and probiotics had a significant effect on ileum and colon. The population of Lactobacillus and Bifidobacterium in the probiotic group was significantly greater than the antibiotic group and the allograft group. The liver injury was significantly reduced in the antibiotic group and the probiotic group compared with the allograft group. The CD4/CD8 and Treg cells in Peyer's patch were decreased in the antibiotic group. The intestinal Treg cell and serum and liver TGF-β were increased markedly while CD4/CD8 ratio was significantly decreased in the probiotic group. It suggested that probiotics mediate their beneficial effects through increase of Treg cells and TGF-β and deduction of CD4/CD8 in rats with acute rejection (AR) after OLT.

摘要

以往的研究都集中在益生菌和抗生素对肝移植后感染的影响上。在此,我们关注益生菌和抗生素引起的肠道微生物群改变对同种异体肝移植后肝损伤的影响。将棕色挪威大鼠每天通过灌胃给予生理盐水、益生菌或抗生素,持续3周。灌胃1周后进行原位肝移植(OLT)。评估肠道微生物群的改变、肝功能和组织病理学、血清和肝脏细胞因子以及外周血和派伊尔结中的T细胞。与同种异体移植组相比,在益生菌组和抗生素组中观察到粪便细菌多样性的明显分离。至于OLT后2周时肠道黏膜微生物群的多样性和肠道病理学,抗生素和益生菌对回肠和结肠有显著影响。益生菌组中乳酸杆菌和双歧杆菌的数量明显高于抗生素组和同种异体移植组。与同种异体移植组相比,抗生素组和益生菌组的肝损伤明显减轻。抗生素组中派伊尔结中的CD4/CD8和调节性T细胞减少。益生菌组中肠道调节性T细胞以及血清和肝脏中的转化生长因子-β明显增加,而CD4/CD8比值明显降低。这表明在OLT后发生急性排斥反应(AR)的大鼠中,益生菌通过增加调节性T细胞和转化生长因子-β以及降低CD4/CD8来介导其有益作用。

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