Hydrogen sulfide attenuates gastric mucosal injury induced by restraint water-immersion stress via activation of KATPchannel and NF-κB dependent pathway

AIMTo explore the effect of hydrogen sulfide (H2S) on restraint water-immersion stress (RWIS)-induced gastric lesions in rats and the influence of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway on such an effect.METHODSMale Wistar rats were randomly divided into a control group, a physiological saline (PS) group, a sodium hydrosulfide (NaHS) group, a glibenclamide (Gl) group, Gl plus NaHS group, a pyrrolidine dithiocarbamate (PDTC) group, and a PDTC plus NaHS group. Gastric mucosal injury was induced by RWIS for 3 h in rats, and gastric mucosal damage was analyzed after that. The PS, NaHS (100 μmol/kg body weight), Gl (100 μmol/kg body weight), Gl (100 μmol/kg or 150 μmol/kg body weight) plus NaHS (100 μmol/kg body weight), PDTC (100 μmol/kg body weight), and PDTC (100 μmol/kg body weight) plus NaHS (100 μmol/kg body weight) were respectively injected intravenously before RWIS.RESULTSRWIS induced serious gastric lesions in the rats in the PS pretreatment group. The pretreatment of NaHS (a H2S donor) significantly reduced the damage induced by RWIS. The gastric protective effect of the NaHS during RWIS was attenuated by PDTC, an NF-κB inhibitor, and also by glibenclamide, an ATP-sensitive potassium channel blocker, in a dose-dependent manner.CONCLUSIONThese results suggest that exogenous H2S plays a protective role against RWIS injury in rats, possibly through modulation of KATP channel opening and the NF-κB dependent pathway.

Nervous mechanisms of restraint water-immersion stress-induced gastric mucosal lesion

Stress-induced gastric mucosal lesion(SGML)is one of the most common visceral complications after trauma.Exploring the nervous mechanisms of SGML has become a research hotspot.Restraint water-immersion stress(RWIS)can induce GML and has been widely used to elucidate the nervous mechanisms of SGML.It is believed that RWIS-induced GML is mainly caused by the enhanced activity of vagal parasympathetic nerves.Many central nuclei,such as the dorsal motor nucleus of the vagus,nucleus of the solitary tract,supraoptic nucleus and paraventricular nucleus of the hypothalamus,mediodorsal nucleus of the thalamus,central nucleus of the amygdala and medial prefrontal cortex,are involved in the formation of SGML in varying degrees.Neurotransmitters/neuromodulators,such as nitric oxide,hydrogen sulfide,vasoactive intestinal peptide,calcitonin gene-related peptide,substance P,enkephalin,5-hydroxytryptamine,acetylcholine,catecholamine,glutamate,γ-aminobutyric acid,oxytocin and arginine vasopressin,can participate in the regulation of stress.However,inconsistent and even contradictory results have been obtained regarding the actual roles of each nucleus in the nervous mechanism of RWIS-induced GML,such as the involvement of different nuclei with the time of RWIS,the different levels of involvement of the sub-regions of the same nucleus,and the diverse signalling molecules,remain to be further elucidated.

A Case of Multiple Hemorrhagic Gastric Ulcers Developed via a Mechanism Similar to Water-Immersion Restraint Stress

In rats, water-immersion restraint stress is a model of experimental ulceration. We encountered a case in which multiple hemorrhagic gastric ulcers formed in the stomach in a setting similar to water-immersion restraint stress. The patient was a 54-year-old man who was found wet on a riverbank and transported by ambulance. Because of hypothermia and renal failure, hemodialysis was performed. Tarry stools were noted and endoscopy revealed the presence of multiple hemorrhagic gastric ulcers;thus, hemostasis was performed end oscopically. During the course, pseudo membranous colitis also developed and was ameliorated with vancomycin. Further, the renal failure and gastric ulcers improved, and the patient was discharged from hospital 25 days later. The reason why he survived more than 2 weeks was the hot summer season and he was not soaked in the river water throughout.

Altered Neuronal Activity in the Central Nucleus of the Amygdala Induced by Restraint Water-Immersion Stress in Rats

Restraint water-immersion stress(RWIS), a compound stress model, has been widely used to induce acute gastric ulceration in rats. A wealth of evidence suggests that the central nucleus of the amygdala(CEA) is a focal region for mediating the biological response to stress. Different stressors induce distinct alterations of neuronal activity in the CEA; however, few studies have reported the characteristics of CEA neuronal activity induced by RWIS. Therefore, we explored this issue using immunohistochemistry and in vivo extracellular single-unit recording. Our results showed that RWIS and restraint stress(RS) differentially changed the c-Fos expression and firing properties of neurons in the medial CEA. In addition,RWIS, but not RS, induced the activation of corticotropinreleasing hormone neurons in the CEA. These findings suggested that specific neuronal activation in the CEA is involved in the formation of RWIS-induced gastric ulcers.This study also provides a possible theoretical explanation for the different gastric dysfunctions induced by different stressors.

Proteomics of the mediodorsal thalamic nucleus of rats with stress-induced gastric ulcer

BACKGROUND Stress-induced gastric ulcer(SGU) is one of the most common visceral complications after trauma. Restraint water-immersion stress(RWIS) can cause serious gastrointestinal dysfunction and has been widely used to study the pathogenesis of SGU to identify medications that can cure the disease. The mediodorsal thalamic nucleus(MD) is the centre integrating visceral and physical activity and contributes to SGU induced by RWIS. Hence, the role of the MD during RWIS needs to be studied.AIM To screen for differentially expressed proteins in the MD of the RWIS rats to further elucidate molecular mechanisms of SGU.METHODS Male Wistar rats were selected randomly and divided into two groups, namely, a control group and an RWIS group. Gastric mucosal lesions of the sacrificed rats were measured using the erosion index and the proteomic profiles of the MD were generated through isobaric tags for relative and absolute quantitation(iTRAQ) coupled with two-dimensional liquid chromatography and tandem mass spectrometry. Additionally, iTRAQ results were verified by Western blot analysis.RESULTS A total of 2853 proteins were identified, and these included 65 dysregulated(31 upregulated and 34 downregulated) proteins(fold change ratio ≥ 1.2). Gene Ontology(GO) analysis showed that most of the upregulated proteins are primarily related to cell division, whereas most of the downregulated proteins are related to neuron morphogenesis and neurotransmitter regulation. Ingenuity Pathway Analysis revealed that the dysregulated proteins are mainly involved in the neurological disease signalling pathways. Furthermore, our results indicated that glycogen synthase kinase-3 beta might be related to the central mechanismthrough which RWIS gives rise to SGU.CONCLUSION Quantitative proteomic analysis elucidated the molecular targets associated with the production of SGU and provides insights into the role of the MD. The underlying molecular mechanisms need to be further dissected.

束缚-浸水应激对大鼠内侧前额叶皮质锥体神经元放电活动的影响

目的 探究大鼠在束缚-浸水应激不同时间段,其内侧前额叶皮质（MPFC）内锥体神经元的电活动情况.方法 利用多通道在体记录技术,记录大鼠在束缚-浸水应激前和应激4h过程中MPFC锥体神经元的单位放电活动,进一步分析其放电频率、放电间隔及爆发式放电活动等指标,研究束缚-浸水应激对MPFC锥体神经元电活动的影响.结果 共采集到了12只大鼠MPFC内的25个锥体神经元的电活动.锥体神经元的电活动表现出两种相反趋势：（1）A类神经元（72％）其放电活动随应激时间的延长而受到抑制,放电率由应激前的（3.57±0.63） Hz持续降低到应激后第4小时的（0.81±0.11） Hz （P＜0.01）;同时簇状波的发放率也由应激前的（10.29±3.04）个/min,持续降低到应激后第4小时的（1.02±0.50）个/min （P＜0.01）,爆发式放电所占比例也显著性减少,变化效应与应激时间成正相关.（2）B类神经元（28％）则表现出短时的兴奋效应,其放电率由应激前的（1.77±0.45） Hz,升高到应激后第2小时的（2.67±0.74） Hz （P＜0.05）,平均放电间隔也明显缩短;簇状波的发放率由应激前的（2.01 ±0.73）个/min,升高到应激后第1小时的（9.04±2.42）个/min（P＜0.05）,爆发式放电所占比例也显著性升高,但B类神经元的兴奋持续时间较短.结论 束缚-浸水应激可改变MPFC内锥体神经元的电活动,A类锥体神经元活动受到抑制,B类锥体神经元活动增强.