PMID- 29680908 OWN - NLM STAT- MEDLINE DCOM- 20181010 LR - 20181114 IS - 1573-2576 (Electronic) IS - 0360-3997 (Linking) VI - 41 IP - 3 DP - 2018 Jun TI - GTS-21 Protected Against LPS-Induced Sepsis Myocardial Injury in Mice Through alpha7nAChR. PG - 1073-1083 LID - 10.1007/s10753-018-0759-x [doi] AB - Sepsis-induced myocardial injury is a well-known cause of mortality. The cholinergic anti-inflammatory pathway (CHAIP) is a physiological mechanism by which the central nervous system regulates immune response through the vagus nerve and acetylcholine; the alpha7-nicotinic acetylcholine receptor (alpha7nAChR) is the main component of CHAIP; GTS-21, a synthetic alpha7nAChR selective agonist, has repeatedly shown its powerful anti-inflammatory effect. However, little is known about its effect on LPS-induced myocardial injury. We investigated the protective effects of GTS-21 on lipopolysaccharide (LPS)-induced cardiomyopathy via the cholinergic anti-inflammatory pathway in a mouse sepsis model. We constructed the model of myocardial injury in sepsis mice by C57BL/6 using LPS and determined the time of LPS treatment by hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). C57BL/6 mice were randomized into five groups: blank control group, model group, alpha-bungarotoxin + LPS group, GTS-21 + LPS group, and alpha-bungarotoxin + GTS-21 + LPS group. The pathological results of myocardial tissue were detected by the HE method; the apoptosis rate was detected by the TUNEL method; the relative expressions of NF-kappaB p65, Caspase-3, Caspase-8, Bcl-2, Bax, p53, and a7nAChR were detected by real-time quantitative PCR (RT-PCR); and the protein expressions of IL-6, IL-1 beta, TNF-alpha, and pSTAT3 were detected by western blot. The results showed that LPS-induced myocardial pathological and apoptosis changes were significant compared with the blank group, which was reversed by GTS-21; however, pretreatment with alpha-bungarotoxin obviously blocked the protective effect of GTS-21. NF-kappaB p65, Caspase-3, Caspase-8, Bax, p53, IL-6, IL-1beta, TNF-alpha, and pSTAT3 were significantly increased in the model group, while a7nAChR and Bcl-2 were significantly decreased; GTS-21 treatment reversed that result, while pretreatment with alpha-bungarotoxin strengthened the result in the model. And pretreatment with alpha-bungarotoxin blocked the protective effect of GTS-21. GTS-21 can alleviate the LPS-induced damage in the heart via a7nAChR, and pretreatment with alpha-bungarotoxin obviously blocked the protective effect of GTS-21 on sepsis in mice. FAU - Kong, Weilan AU - Kong W AD - Department of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Road, Harbin, 150001, China. FAU - Kang, Kai AU - Kang K AD - Department of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Road, Harbin, 150001, China. FAU - Gao, Yang AU - Gao Y AD - Department of Critical Care Medicine, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150086, China. FAU - Liu, Haitao AU - Liu H AD - Department of Critical Care Medicine, the Cancer Hospital of Harbin Medical University, 150 Haping Road, Harbin, 150081, China. FAU - Meng, Xianglin AU - Meng X AD - Department of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Road, Harbin, 150001, China. FAU - Cao, Yanhui AU - Cao Y AD - Department of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Road, Harbin, 150001, China. FAU - Yang, Songliu AU - Yang S AD - Department of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Road, Harbin, 150001, China. FAU - Liu, Wen AU - Liu W AD - Department of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Road, Harbin, 150001, China. FAU - Zhang, Jiannan AU - Zhang J AD - Department of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Road, Harbin, 150001, China. FAU - Yu, Kaijiang AU - Yu K AD - Department of Critical Care Medicine, the Cancer Hospital of Harbin Medical University, 150 Haping Road, Harbin, 150081, China. drkaijiang1@126.com. AD - Institute of Critical Care Medicine in Sino Russian Medical Research Center of Harbin Medical University, 150 Haping Road, Harbin, 150081, China. drkaijiang1@126.com. FAU - Zhao, Mingyan AU - Zhao M AD - Department of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Road, Harbin, 150001, China. mingyanzhao1970@163.com. LA - eng PT - Journal Article PL - United States TA - Inflammation JT - Inflammation JID - 7600105 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Benzylidene Compounds) RN - 0 (Bungarotoxins) RN - 0 (Lipopolysaccharides) RN - 0 (Pyridines) RN - 0 (alpha7 Nicotinic Acetylcholine Receptor) RN - 8S399XDN2K (3-(2,4-dimethoxybenzylidene)anabaseine) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology MH - Apoptosis/drug effects MH - Benzylidene Compounds/*pharmacology MH - Bungarotoxins/pharmacology MH - Heart Injuries/*chemically induced MH - Lipopolysaccharides/pharmacology MH - Mice MH - Mice, Inbred C57BL MH - Pyridines/*pharmacology MH - Sepsis/*drug therapy MH - alpha7 Nicotinic Acetylcholine Receptor/agonists/analysis/antagonists & inhibitors OTO - NOTNLM OT - GTS-21 OT - a7nAChR OT - cholinergic anti-inflammatory OT - sepsis EDAT- 2018/04/24 06:00 MHDA- 2018/10/12 06:00 CRDT- 2018/04/23 06:00 PHST- 2018/04/24 06:00 [pubmed] PHST- 2018/10/12 06:00 [medline] PHST- 2018/04/23 06:00 [entrez] AID - 10.1007/s10753-018-0759-x [pii] AID - 10.1007/s10753-018-0759-x [doi] PST - ppublish SO - Inflammation. 2018 Jun;41(3):1073-1083. doi: 10.1007/s10753-018-0759-x.