Down-regulation of circDMNT3B is conducive to intestinal mucosal permeability dysfunction of rats with sepsis via sponging miR-20b-5p

Down-regulation of circDMNT3B is conducive to intestinal mucosal permeability dysfunction of rats with sepsis via sponging miR-20b-5p
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circDMNT3B下调通过海绵miR-20b-5p有利于脓毒症大鼠肠黏膜通透性功能障碍

DOI:
10.1111/jcmm.15324
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发表时间:
2020-05-07
影响因子:
5.3
通讯作者:
Chen Dechang
Chen Dechang
中科院分区:
医学2区
文献类型:
--
作者:
Liu Jiao;Liu Yongan;Chen Dechang

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Sepsis is a life-threatening syndrome with a high risk of mortality, which is caused by the dysregulated host response to infection. We examined significant roles of circDMNT3B and miR-20b-5p in the intestinal mucosal permeability dysfunction of rats with sepsis. SD rats were randomly divided into 6 groups (n = 10/group): sham group, sepsis group, si-negative control group, circDNMT3B-si1 group, circDNMT3B-si2 group and circDNMT3B-si1 + anti-miR-20b-5p group. The level of malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, interleukin (IL)-6 and IL-10 levels were measured through ELISA assay kits. Cell survival rate and cell apoptosis were evaluated by Cell-Counting Kit-8 Assay and flow cytometry, respectively. Luciferase reporter assays were used to investigate interactions between miR-20b-5p circDMNT3B in HEK-293T cells. Silencing circDNMT3B can significantly increase the level of d-lactic acid, FD-40, MDA, diamine oxidase, IL-10 and IL-6, compared with sepsis group, while the SOD activity was lower. Silencing circDNMT3B leads to oxidative damage and influence inflammatory factors level in intestinal tissue. CircDNMT3B was identified as a target gene of miR-20b-5p. Silencing circDNMT3B decreased cell survival and induced apoptosis in Caco2 cells treated with LPS, which was reversed by anti-miR-20b-5p. MiR-20b-5p inhibitor remarkably down-regulated mentioned-above levels, in addition to up-regulate SOD activity, which may relieve the damage of intestinal mucosal permeability caused by silencing circDNMT3B in sepsis rats. Down-regulation of circDMNT3B was conducive to the dysfunction of intestinal mucosal permeability via sponging miR-20b-5p in sepsis rats, which may provide the novel strategy for sepsis treatment in the future.