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 restrai...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.展开更多
BACKGROUND Stress-related gastric mucosal damage or ulcer remains an unsolved issue for critically ill patients.Stress ulcer prophylaxis has been part of routine intensive care,but uncertainty and controversy still ex...BACKGROUND Stress-related gastric mucosal damage or ulcer remains an unsolved issue for critically ill patients.Stress ulcer prophylaxis has been part of routine intensive care,but uncertainty and controversy still exist.Co-secreted with mucins,intestinal trefoil factor(ITF)is reported to promote restitution and regeneration of intestinal mucosal epithelium,although the mechanism remains unknown.AIM To elucidate the protective effects of ITF on gastric mucosa and explore the possible mechanisms.METHODS We used a rat model of gastric mucosal damage induced by water immersion restraint stress and lipopolysaccharide-treated human gastric epithelial cell line to investigate the potential effects of ITF on damaged gastric mucosa both in vivo and in vitro.RESULTS ITF promoted the proliferation and migration and inhibited necrosis of gastric mucosal epithelia in vitro.It also preserved the integrity of gastric mucosa by upregulating expressions of occludin and zonula occludens-1.In the rat model,pretreatment with ITF ameliorated the gastric mucosal epithelial damage and facilitated mucosal repair.The protective effects of ITF were confirmed to be exerted via activation of Akt signaling,and the specific inhibitor of Akt signaling LY249002 reversed the protective effects.CONCLUSION ITF might be a promising candidate for prevention and treatment of stressinduced gastric mucosal damage,and further studies should be undertaken to verify its clinical feasibility.展开更多
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 ...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.展开更多
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 use...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.展开更多
目的探讨辣椒素(capsaicin,CAP)对水浸-束缚应激(water immersion restraint stress,WIRS)大鼠胃动力的作用及机制。方法雄性SD大鼠30只,随机分为3组:正常对照组、WIRS模型组、CAP干预组。其中正常对照组自由摄食进水;WIRS模型组每日WIR...目的探讨辣椒素(capsaicin,CAP)对水浸-束缚应激(water immersion restraint stress,WIRS)大鼠胃动力的作用及机制。方法雄性SD大鼠30只,随机分为3组:正常对照组、WIRS模型组、CAP干预组。其中正常对照组自由摄食进水;WIRS模型组每日WIRS 1 h后自由摄食进水;CAP干预组每日WIRS 1 h后喂食CAP饲料。4周后所有大鼠给予酚红溶液灌胃后麻醉处死,测定胃酚红排空率;采用ELISA法检测血浆胃动素(motilin,MTL)水平;采用免疫组化方法检测胃窦辣椒素受体(transient receptor potential vanilloid1,TRPV1)、P物质(substance P,SP)的表达;用RT-PCR方法检测c-kit m RNA、SCF m RNA的转录水平。结果大鼠胃酚红排空率:WIRS模型组胃酚红排空率显著低于其余两组(P<0.05);正常对照组胃酚红排空率与CAP干预组相比,差异无统计学意义(P>0.05)。血浆MTL水平:WIRS模型组血浆MTL水平显著低于其余两组(P<0.05);正常对照组血浆MTL水平显著低于CAP干预组(P<0.05)。免疫组化结果:大鼠胃窦组织TRPV1表达积分:CAP干预组TRPV1表达水平显著高于其余两组(P<0.05);正常对照组TRPV1表达水平与WIRS模型组相比,差异无统计学意义(P>0.05)。大鼠胃窦组织SP表达积分:WIRS模型组SP表达水平显著低于其余两组(P<0.05);正常对照组SP表达水平显著低于CAP干预组(P<0.05)。RT-PCR方法检测结果:大鼠胃窦组织c-kit m RNA表达结果:WIRS模型组c-kit m RNA转录水平显著低于正常对照组(P<0.05);正常对照组、WIRS模型组c-kit m RNA转录水平与CAP干预组相比,差异无统计学意义(P>0.05)。大鼠胃窦组织SCF m RNA表达结果:WIRS模型组SCF m RNA转录水平显著低于其余两组(P<0.05);正常对照组SCF m RNA转录水平显著低于CAP干预组(P<0.05)。结论 CAP可能对WIRS大鼠胃动力具有改善作用,其机制可能与CAP调节TRPV1、SP的表达及MTL的释放有关,是否与Cajal间质细胞相关尚不明确。展开更多
目的:研究不同时程低强度束缚水浸应激对大鼠Cajal间质细胞(interstitial cells of Cajal,ICC)数量的影响,探讨慢性应激导致胃动力改变与ICC的相关性.方法:雄性SPF级SD大鼠48只被随机分为6组,即实验3d、7d、28d组和对照3d、7d、28d组,每...目的:研究不同时程低强度束缚水浸应激对大鼠Cajal间质细胞(interstitial cells of Cajal,ICC)数量的影响,探讨慢性应激导致胃动力改变与ICC的相关性.方法:雄性SPF级SD大鼠48只被随机分为6组,即实验3d、7d、28d组和对照3d、7d、28d组,每组8只.实验组23℃水域箱内束缚水浸1h/d,对照组自由摄食饮水.4d、8d、29d晨序贯脱颈处死.取膜胃小弯侧(ICC-1)、腺胃小弯侧(ICC-3)、腺胃大弯侧上1/3处(ICC-5)、腺胃幽门旁0.5cm处(ICC-7)组织各一块放入固定液中,制成石蜡切片;抗c-kit免疫组织化学染色,观察不同层次ICC计数.结果:正常大鼠胃内ICC主要分布在肌内(ICC-MY)和肌间(ICC-IM),而黏膜下(ICC-SM)和深肌丛(ICC-DMP)较少.实验3d组的各层ICC数量与对照组相比无明显差异,实验7d和28d组大鼠不同部位、不同层次及同一部位不同层次ICC数量明显异于同期对照组.应激时间长短对不同部位不同层次及同一部位不同层次ICC总数有明显影响,其大致规律是先正常后增加再减少,即先升高后降低.应激主要引起ICC-MY及ICC-IM数量发生变化,而本来较少的ICC-SM和ICC-DMP受影响较轻.结论:长时间低强度的慢性束缚水浸应激可以使大鼠胃窦ICC数量发生变化.展开更多
文摘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.
基金Social Development Projects of Jiangsu Province,No.BE2017720the National Natural Science Foundation of China,No.81701894+4 种基金Jiangsu Provincial Medical Youth Talent,No.QNRC2016909 and No.QNRC2016908Natural Science Foundation of Jiangsu Province,No.BK20190247Science Foundation of Jiangsu Health Commission,No.H2018039China Postdoctoral Science Foundation,No.2018M643890Jiangsu Postdoctoral Science Foundation,No.2018K048A and No.2020Z193。
文摘BACKGROUND Stress-related gastric mucosal damage or ulcer remains an unsolved issue for critically ill patients.Stress ulcer prophylaxis has been part of routine intensive care,but uncertainty and controversy still exist.Co-secreted with mucins,intestinal trefoil factor(ITF)is reported to promote restitution and regeneration of intestinal mucosal epithelium,although the mechanism remains unknown.AIM To elucidate the protective effects of ITF on gastric mucosa and explore the possible mechanisms.METHODS We used a rat model of gastric mucosal damage induced by water immersion restraint stress and lipopolysaccharide-treated human gastric epithelial cell line to investigate the potential effects of ITF on damaged gastric mucosa both in vivo and in vitro.RESULTS ITF promoted the proliferation and migration and inhibited necrosis of gastric mucosal epithelia in vitro.It also preserved the integrity of gastric mucosa by upregulating expressions of occludin and zonula occludens-1.In the rat model,pretreatment with ITF ameliorated the gastric mucosal epithelial damage and facilitated mucosal repair.The protective effects of ITF were confirmed to be exerted via activation of Akt signaling,and the specific inhibitor of Akt signaling LY249002 reversed the protective effects.CONCLUSION ITF might be a promising candidate for prevention and treatment of stressinduced gastric mucosal damage,and further studies should be undertaken to verify its clinical feasibility.
基金supported by the National Natural Science Foundation of China (31571104 and 81501149)the Science and Technological Project of Shandong Province of China (2016GSF201058)
文摘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.
基金Supported by National Natural Science Foundation of China,No.31501861Natural Science Foundation of Shandong Province,China,No.ZR2015CM013
文摘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.
文摘目的探讨辣椒素(capsaicin,CAP)对水浸-束缚应激(water immersion restraint stress,WIRS)大鼠胃动力的作用及机制。方法雄性SD大鼠30只,随机分为3组:正常对照组、WIRS模型组、CAP干预组。其中正常对照组自由摄食进水;WIRS模型组每日WIRS 1 h后自由摄食进水;CAP干预组每日WIRS 1 h后喂食CAP饲料。4周后所有大鼠给予酚红溶液灌胃后麻醉处死,测定胃酚红排空率;采用ELISA法检测血浆胃动素(motilin,MTL)水平;采用免疫组化方法检测胃窦辣椒素受体(transient receptor potential vanilloid1,TRPV1)、P物质(substance P,SP)的表达;用RT-PCR方法检测c-kit m RNA、SCF m RNA的转录水平。结果大鼠胃酚红排空率:WIRS模型组胃酚红排空率显著低于其余两组(P<0.05);正常对照组胃酚红排空率与CAP干预组相比,差异无统计学意义(P>0.05)。血浆MTL水平:WIRS模型组血浆MTL水平显著低于其余两组(P<0.05);正常对照组血浆MTL水平显著低于CAP干预组(P<0.05)。免疫组化结果:大鼠胃窦组织TRPV1表达积分:CAP干预组TRPV1表达水平显著高于其余两组(P<0.05);正常对照组TRPV1表达水平与WIRS模型组相比,差异无统计学意义(P>0.05)。大鼠胃窦组织SP表达积分:WIRS模型组SP表达水平显著低于其余两组(P<0.05);正常对照组SP表达水平显著低于CAP干预组(P<0.05)。RT-PCR方法检测结果:大鼠胃窦组织c-kit m RNA表达结果:WIRS模型组c-kit m RNA转录水平显著低于正常对照组(P<0.05);正常对照组、WIRS模型组c-kit m RNA转录水平与CAP干预组相比,差异无统计学意义(P>0.05)。大鼠胃窦组织SCF m RNA表达结果:WIRS模型组SCF m RNA转录水平显著低于其余两组(P<0.05);正常对照组SCF m RNA转录水平显著低于CAP干预组(P<0.05)。结论 CAP可能对WIRS大鼠胃动力具有改善作用,其机制可能与CAP调节TRPV1、SP的表达及MTL的释放有关,是否与Cajal间质细胞相关尚不明确。
文摘目的:研究不同时程低强度束缚水浸应激对大鼠Cajal间质细胞(interstitial cells of Cajal,ICC)数量的影响,探讨慢性应激导致胃动力改变与ICC的相关性.方法:雄性SPF级SD大鼠48只被随机分为6组,即实验3d、7d、28d组和对照3d、7d、28d组,每组8只.实验组23℃水域箱内束缚水浸1h/d,对照组自由摄食饮水.4d、8d、29d晨序贯脱颈处死.取膜胃小弯侧(ICC-1)、腺胃小弯侧(ICC-3)、腺胃大弯侧上1/3处(ICC-5)、腺胃幽门旁0.5cm处(ICC-7)组织各一块放入固定液中,制成石蜡切片;抗c-kit免疫组织化学染色,观察不同层次ICC计数.结果:正常大鼠胃内ICC主要分布在肌内(ICC-MY)和肌间(ICC-IM),而黏膜下(ICC-SM)和深肌丛(ICC-DMP)较少.实验3d组的各层ICC数量与对照组相比无明显差异,实验7d和28d组大鼠不同部位、不同层次及同一部位不同层次ICC数量明显异于同期对照组.应激时间长短对不同部位不同层次及同一部位不同层次ICC总数有明显影响,其大致规律是先正常后增加再减少,即先升高后降低.应激主要引起ICC-MY及ICC-IM数量发生变化,而本来较少的ICC-SM和ICC-DMP受影响较轻.结论:长时间低强度的慢性束缚水浸应激可以使大鼠胃窦ICC数量发生变化.
