PMID- 34081253 OWN - NLM STAT- MEDLINE DCOM- 20220202 LR - 20220202 IS - 1573-2576 (Electronic) IS - 0360-3997 (Linking) VI - 44 IP - 5 DP - 2021 Oct TI - Propofol Regulates the TLR4/NF-kappaB Pathway Through miRNA-155 to Protect Colorectal Cancer Intestinal Barrier. PG - 2078-2090 LID - 10.1007/s10753-021-01485-0 [doi] AB - Surgery for colorectal cancer (CRC) can cause damage to the intestinal mucosal barrier and lead to bacterial invasion. This study mainly analyzed whether propofol (PPF) could protect the intestinal mucosal barrier damage caused by CRC surgery, and explored its molecular mechanism. A mouse CRC model was constructed using azomethane and dextran sulfate sodium. During anesthesia, continuous intravenous injection of PPF was used for intervention. The influences of PPF on intestinal mucosal permeability and bacterial invasion were detected. The levels of microRNA (miR)-155, Toll-like receptor 4 (TLR4)/NF-kappaB in the intestinal mucosa, and the location of miR-155 were detected by fluorescence in situ hybridization (FISH). Mouse macrophages were used to analyze the regulation of miR-155 on the secretion of inflammatory cytokines through the TLR4/NF-kappaB pathway. PPF treatment promoted the expression of tight junction protein in the intestinal mucosa, protected the intestinal barrier, inhibited the translocation of intestinal bacteria, and increased the level of the beneficial bacterium Lactobacillus on the mucosal surface. In addition, PPF treatment could inhibit the expression of miR-155, TLR4/NF-KB, and reverse inflammatory response. miR-155 was expressed in macrophages of intestinal mucosa tissue. Overexpression of miR-155 promoted the nuclear translocation of NF-kappaB and the expression of inflammatory cytokines in macrophages. The use of VIPER to inhibit TLR4 reversed the pro-inflammatory effects of miR-155. PPF might inhibit the activation of the NF-kappaB pathway by downregulating miR-155 expression, thereby reducing the secretion of inflammatory cytokines. This might be the mechanism by which PPF protected the intestinal barrier of CRC surgical model mice. CI - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Gao, Yuhua AU - Gao Y AD - Department of Anesthesiology, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqing District, Yinchuan, 750004, Ningxia, China. AD - School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, China. FAU - Han, Tao AU - Han T AD - Department of Ultrasound, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China. FAU - Han, Cailing AU - Han C AD - Department of Anesthesiology, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqing District, Yinchuan, 750004, Ningxia, China. FAU - Sun, Hua AU - Sun H AD - Department of Anesthesiology, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqing District, Yinchuan, 750004, Ningxia, China. FAU - Yang, Xiaoxia AU - Yang X AD - Department of Anesthesiology, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqing District, Yinchuan, 750004, Ningxia, China. FAU - Zhang, Dongmei AU - Zhang D AD - Department of Anesthesiology, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqing District, Yinchuan, 750004, Ningxia, China. FAU - Ni, Xinli AU - Ni X AUID- ORCID: 0000-0002-1330-3620 AD - Department of Anesthesiology, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqing District, Yinchuan, 750004, Ningxia, China. xinlini6@nyfy.com.cn. LA - eng GR - 2019A0206/Natural Science Foundation of Ningxia Province/ GR - XM2018170/Ningxia Medical University Foundation Project/ PT - Journal Article DEP - 20210603 PL - United States TA - Inflammation JT - Inflammation JID - 7600105 RN - 0 (Hypnotics and Sedatives) RN - 0 (Inflammation Mediators) RN - 0 (MicroRNAs) RN - 0 (Mirn155 microRNA, mouse) RN - 0 (NF-kappa B) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 4) RN - YI7VU623SF (Propofol) SB - IM MH - Animals MH - Colorectal Neoplasms/drug therapy/*metabolism/pathology MH - Hypnotics and Sedatives/pharmacology/therapeutic use MH - Inflammation Mediators/antagonists & inhibitors/metabolism MH - Intestinal Mucosa/drug effects/*metabolism/pathology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/*antagonists & inhibitors/metabolism MH - NF-kappa B/*antagonists & inhibitors/metabolism MH - Propofol/pharmacology/*therapeutic use MH - RAW 264.7 Cells MH - Signal Transduction/drug effects/physiology MH - Toll-Like Receptor 4/*antagonists & inhibitors/metabolism OTO - NOTNLM OT - Toll-like receptor 4 (TLR4)/NF-kappaB OT - colorectal cancer OT - intestinal barrier OT - microRNA-155 OT - propofol EDAT- 2021/06/04 06:00 MHDA- 2022/02/03 06:00 CRDT- 2021/06/03 12:31 PHST- 2021/04/08 00:00 [received] PHST- 2021/05/23 00:00 [accepted] PHST- 2021/05/11 00:00 [revised] PHST- 2021/06/04 06:00 [pubmed] PHST- 2022/02/03 06:00 [medline] PHST- 2021/06/03 12:31 [entrez] AID - 10.1007/s10753-021-01485-0 [pii] AID - 10.1007/s10753-021-01485-0 [doi] PST - ppublish SO - Inflammation. 2021 Oct;44(5):2078-2090. doi: 10.1007/s10753-021-01485-0. Epub 2021 Jun 3.