title: Protective effect of histamine microinjected into cerebellar fastigial nucleus on stress gastric mucosal damage in rats.
abstract: In the study, we investigated the effect of histamine microinjected into cerebellar fastigial nucleus (FN) on stress gastric mucosal damage (SGMD), and its mechanisms in rats. The model of SGMD was established by restraining and water (21±1°C)-immersion for 3h. The gastric mucosal damage index (GMDI) indicated the severity of gastric mucosal damage. Histamine or receptor antagonist was microinjected into the FN. The decussation of superior cerebellar peduncle (DSCP) and the lateral hypothalamic area (LHA) were destroyed, respectively. The pathological changes of gastric mucosa were evaluated using biological signal acquisition system, Laser-Doppler flowmeter, and western blotting. We found that the microinjection of histamine (0.05, 0.5, and 5μg) into FN significantly attenuated the SGMD, in a dose-dependent manner, whereas, the microinjection of histamine H2 receptor antagonist, ranitidine, and glutamic acid decarboxylase antagonist, 3-mercaptopropionic acid (3-MPA) exacerbated the SGMD. The protective effect of histamine on SGMD was abolished by electrical lesion of DSCP or chemical ablation of LHA. The microinjection of histamine decreased the discharge frequency of the greater splanchnic nerve, and the gastric mucosal blood flow was increased. In addition, the cellular proliferation was enhanced, but the cellular apoptosis was reduced in the gastric mucosa. Also the pro-apoptosis protein, Bax, and caspase-3 were down-regulated, and the anti-apoptosis protein, Bcl-2 was up-regulated following microinjection of histamine. In conclusion, the FN participated in the regulation of SGMD after histamine microinjected into FN, and cerebellar-hypothalamic circuits (include: DSCP, LHA) contribute to the process, which may provide a new therapeutic strategy for SGMD.
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical College, 99 West Huaihai Road, Xuzhou 221002, Jiangsu, China; Department of Physiology, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou 221002, Jiangsu, China; Department of Gastroenterology, The Affiliated Huai'an Hospital of Xuzhou Medical College, 62 South Huaihai Road, Huai'an 223002, Jiangsu, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Qiao
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical College, 99 West Huaihai Road, Xuzhou 221002, Jiangsu, China; Department of Physiology, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou 221002, Jiangsu, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical College, 99 West Huaihai Road, Xuzhou 221002, Jiangsu, China. Electronic address: feisj99@xzmc.edu.cn.
authors.forename: Su-Juan
authors.initials: SJ
authors.lastname: Fei
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical College, 99 West Huaihai Road, Xuzhou 221002, Jiangsu, China; Department of Physiology, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou 221002, Jiangsu, China.
authors.forename: Jin-Zhou
authors.initials: JZ
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical College, 99 West Huaihai Road, Xuzhou 221002, Jiangsu, China; Department of Physiology, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou 221002, Jiangsu, China.
authors.forename: Sheng-Ping
authors.initials: SP
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical College, 99 West Huaihai Road, Xuzhou 221002, Jiangsu, China; Department of Physiology, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou 221002, Jiangsu, China.
authors.forename: Zhang-Bo
authors.initials: ZB
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical College, 99 West Huaihai Road, Xuzhou 221002, Jiangsu, China; Department of Physiology, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou 221002, Jiangsu, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical College, 99 West Huaihai Road, Xuzhou 221002, Jiangsu, China; Department of Physiology, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou 221002, Jiangsu, China. Electronic address: jfzhang@xzmc.edu.cn.
authors.forename: Jian-Fu
authors.initials: JF
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006632:Histamine / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008845:Microinjections; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism* / Q000517:prevention & control*
chemical_list: D018696:Neuroprotective Agents; D006632:Histamine
keywords: Decussation of superior cerebellar peduncle; Fastigial nucleus; Histamine; Lateral hypothalamic area; Stress-induced gastric mucosal damage