液压打击致应激性溃疡大鼠下丘脑IL-6表达及胃粘膜c-Jun氨基末端激酶（JNK）信号通路改变的实验研究
|
摘要
目的:本实验拟通过建立大鼠颅脑外伤致应激性溃疡模型,探讨(1)胃粘膜血流量、胃液PH值与胃粘膜损伤指数的关系;(2)中枢白介素6在应激大鼠下丘脑的表达,以及参与应激性溃疡发生的机制;(3)c-Jun氨基末端激酶(JNK)信号通路激活是否参与了应激性溃疡的形成,以及其通路抑制剂能否减轻胃粘膜的损伤。
方法:采用液压打击法建立大鼠颅脑外伤并发应激性溃疡模型,将20只雄性SD大鼠随机等分为对照组、致伤1小时组、致伤6小时组和致伤12小时组,每组5只,测定各组大鼠胃液PH值、胃粘膜血流量、胃粘膜损伤指数,并观察胃粘膜大体及光镜下组织病理学变化。采用免疫组化、Westernblot的方法检测致伤后下丘脑中枢性白介素6的表达与分布;致伤后胃粘膜p-JNK的表达与分布。设立抑制剂组,通过观测抑制剂组胃液PH值、胃粘膜血流量、胃粘膜损伤指数以及胃粘膜大体及光镜下组织病理学变化,明确抑制剂能减轻胃粘膜损伤的作用。
结果:(1)致伤后1小时即出现胃粘膜损伤,并且胃粘膜损伤指数随时间的延长而不断增加,损伤程度不断加重;致伤后1小时有血流量的暂时性增加,处于波峰,此后逐渐下降,6小时后趋于平稳,但致伤后6小时和12小时组仍较对照组降低;致伤后1小时胃液PH值明显降低,此后PH值继续下降,到致伤后6小时处于最低点,致伤后12小时胃液PH值较致伤后1小时和6小时有升高,但各组较对照组仍有明显降低;应激性溃疡大鼠胃液PH值与胃粘膜损伤指数不呈完全线性负相关,但各实验组胃液PH值较对照组有明显减低,而胃粘膜血流量与胃粘膜损伤指数呈负相关。(2)IL-6免疫反应阳性细胞广泛分布于应激大鼠下丘脑水平的神经细胞中,在室旁核附近分布尤为密集。(3)免疫组化发现在溃疡损伤部位组织上皮细胞p-JNK呈强烈阳性反应,c-Jun氨基末端激酶(JNK)信号通路抑制剂SP600125干预能显著减轻胃粘膜的损伤。
结论:(1)本实验通过液压打击致颅脑外伤后建立了脑外伤后应激性溃疡模型。(2)应激性溃疡大鼠胃液PH值与胃粘膜损伤指数不呈完全线性负相关,但各实验组胃液PH值较对照组有明显减低,而胃粘膜血流量与胃粘膜损伤指数呈负相关。(3)中枢IL-6在液压打击致应激性溃疡大鼠下丘脑室旁核(PVN)附近有明显表达,其可能是通过室旁核(PVN)介导中枢胆碱能神经元的兴奋,HPA轴的激活以及5-HT系统的代谢增强,参与应激过程中应激性溃疡发生的某种病理生理机制。(4)在应激性溃疡中c-Jun氨基末端激酶(JNK)信号通路被激活,参与了应激性溃疡的发生。(5)JNK信号通路抑制剂SP600125可改善应激性溃疡大鼠胃粘膜的损伤,JNK信号通路抑制剂作为一种有效的手段,有可能对今后应激性溃疡的治疗提供了新的治疗思路,为临床药物的开发提供了重要指引,可能预示着新的治疗策略。
Objective:Through the establishment of stress ulcer model of the rats induced by traumatic brain injury in the study,we want to know:(1) the relationship between gastric mucosal blood flow,gastric juice PH value and gastric mucosal injury index;(2)the expression of Central interleukin-6 in the rat hypothalamus stress,as well as the mechanism in stress ulceration;(3) C-Jun N-terminal kinase(JNK) signal pathway is or not involved in the activation of stress ulcer formation,as well as its pathway inhibitors can or can't reduce gastric mucosal injury.
Methods:stress ulcer model is established by fluid percussing injury.20 male SD rats were randomly divided into control group,one hour group,six hours group and 12 hours group after injuried(n=5).In each group of rats gastric PH value,gastric mucosal blood flow,gastric mucosal injury index are measured,and observed the histology of gastric mucosa.The expression and distribution of IL-6 in hypothalamus and p-JNK in gastric mucosal are detected by Immunohistochemistry and Westernblot.We establish a inhibitor group in order to know whether inhibitors can or not reduce gastric mucosal injury by the observation of PH value,gastric mucosal blood flow,and the histology.
Results:(1) One hour after injury,we found the injury in the gastric mucosa.And the condition of injury became worse as time passed.The UI was increased.One hour after the injury there was a temporary increase in blood flow.It's the peak.Then the blood flow was declined and keeped stabilizing.But the blood flow was still lower than the blood flow of control group.One hour after the injury the PH value was rapidly declined.The the lowest point was at 6h.Then it was increased.But the PH value of experimental groups was obviously lower than the PH value of control group.They had no negative correlations between PH value of gastric juice and gastric mucosal injury.But the PH value of experimental groups was obviously lower.It shows potential negative correlations between the gastric mucosal blood flow and gastric mucosa damage.(2)IL-6 immunoreactive cells widely distributed in nerve cells of hypothalamus in the stressed rat,especially in the paraventricular nucleus.(3) We found in the epithelial cells of ulcer injury p-JNK was strongly positive response by Immunohistochemistry.c-Jun N-terminal kinase(JNK) signal pathway inhibitor SP600125 can significantly reduce gastric mucosal injury.
Conclusion:(1) stress ulcer model is established by fluid percussing injury.(2) They had no negative correlations between PH value of gastric juice and gastric mucosal injury.But the PH value of experimental groups was obviously lower than the PH value of control group.It shows potential negative correlations between the gastric mucosal blood flow and gastric mucosa damage.(3) The expression of IL-6 near the hypothalamic paraventricular nucleus (PVN) was obvious,which may be through the paraventricular nucleus(PVN) mediated by the central cholinergic neurons excited,HPA axis,as well as the activation of 5-HT system metabolism increased stress involved in the process of stress ulceration in some pathophysiological mechanism.(4) The c-Jun N-terminal kinase(JNK) signal pathway is activated in Stress ulcer and participated in the occurrence of stress ulcer.(5) JNK signaling pathway inhibitors SP600125 reduce gastric mucosa damage of the rat in stress ulcer.As an effective means,it probably provide us a new idea of the treatment of stress ulcer.It maybe provide us very important guidelines for a new treatment strategy.
方法:采用液压打击法建立大鼠颅脑外伤并发应激性溃疡模型,将20只雄性SD大鼠随机等分为对照组、致伤1小时组、致伤6小时组和致伤12小时组,每组5只,测定各组大鼠胃液PH值、胃粘膜血流量、胃粘膜损伤指数,并观察胃粘膜大体及光镜下组织病理学变化。采用免疫组化、Westernblot的方法检测致伤后下丘脑中枢性白介素6的表达与分布;致伤后胃粘膜p-JNK的表达与分布。设立抑制剂组,通过观测抑制剂组胃液PH值、胃粘膜血流量、胃粘膜损伤指数以及胃粘膜大体及光镜下组织病理学变化,明确抑制剂能减轻胃粘膜损伤的作用。
结果:(1)致伤后1小时即出现胃粘膜损伤,并且胃粘膜损伤指数随时间的延长而不断增加,损伤程度不断加重;致伤后1小时有血流量的暂时性增加,处于波峰,此后逐渐下降,6小时后趋于平稳,但致伤后6小时和12小时组仍较对照组降低;致伤后1小时胃液PH值明显降低,此后PH值继续下降,到致伤后6小时处于最低点,致伤后12小时胃液PH值较致伤后1小时和6小时有升高,但各组较对照组仍有明显降低;应激性溃疡大鼠胃液PH值与胃粘膜损伤指数不呈完全线性负相关,但各实验组胃液PH值较对照组有明显减低,而胃粘膜血流量与胃粘膜损伤指数呈负相关。(2)IL-6免疫反应阳性细胞广泛分布于应激大鼠下丘脑水平的神经细胞中,在室旁核附近分布尤为密集。(3)免疫组化发现在溃疡损伤部位组织上皮细胞p-JNK呈强烈阳性反应,c-Jun氨基末端激酶(JNK)信号通路抑制剂SP600125干预能显著减轻胃粘膜的损伤。
结论:(1)本实验通过液压打击致颅脑外伤后建立了脑外伤后应激性溃疡模型。(2)应激性溃疡大鼠胃液PH值与胃粘膜损伤指数不呈完全线性负相关,但各实验组胃液PH值较对照组有明显减低,而胃粘膜血流量与胃粘膜损伤指数呈负相关。(3)中枢IL-6在液压打击致应激性溃疡大鼠下丘脑室旁核(PVN)附近有明显表达,其可能是通过室旁核(PVN)介导中枢胆碱能神经元的兴奋,HPA轴的激活以及5-HT系统的代谢增强,参与应激过程中应激性溃疡发生的某种病理生理机制。(4)在应激性溃疡中c-Jun氨基末端激酶(JNK)信号通路被激活,参与了应激性溃疡的发生。(5)JNK信号通路抑制剂SP600125可改善应激性溃疡大鼠胃粘膜的损伤,JNK信号通路抑制剂作为一种有效的手段,有可能对今后应激性溃疡的治疗提供了新的治疗思路,为临床药物的开发提供了重要指引,可能预示着新的治疗策略。
Objective:Through the establishment of stress ulcer model of the rats induced by traumatic brain injury in the study,we want to know:(1) the relationship between gastric mucosal blood flow,gastric juice PH value and gastric mucosal injury index;(2)the expression of Central interleukin-6 in the rat hypothalamus stress,as well as the mechanism in stress ulceration;(3) C-Jun N-terminal kinase(JNK) signal pathway is or not involved in the activation of stress ulcer formation,as well as its pathway inhibitors can or can't reduce gastric mucosal injury.
Methods:stress ulcer model is established by fluid percussing injury.20 male SD rats were randomly divided into control group,one hour group,six hours group and 12 hours group after injuried(n=5).In each group of rats gastric PH value,gastric mucosal blood flow,gastric mucosal injury index are measured,and observed the histology of gastric mucosa.The expression and distribution of IL-6 in hypothalamus and p-JNK in gastric mucosal are detected by Immunohistochemistry and Westernblot.We establish a inhibitor group in order to know whether inhibitors can or not reduce gastric mucosal injury by the observation of PH value,gastric mucosal blood flow,and the histology.
Results:(1) One hour after injury,we found the injury in the gastric mucosa.And the condition of injury became worse as time passed.The UI was increased.One hour after the injury there was a temporary increase in blood flow.It's the peak.Then the blood flow was declined and keeped stabilizing.But the blood flow was still lower than the blood flow of control group.One hour after the injury the PH value was rapidly declined.The the lowest point was at 6h.Then it was increased.But the PH value of experimental groups was obviously lower than the PH value of control group.They had no negative correlations between PH value of gastric juice and gastric mucosal injury.But the PH value of experimental groups was obviously lower.It shows potential negative correlations between the gastric mucosal blood flow and gastric mucosa damage.(2)IL-6 immunoreactive cells widely distributed in nerve cells of hypothalamus in the stressed rat,especially in the paraventricular nucleus.(3) We found in the epithelial cells of ulcer injury p-JNK was strongly positive response by Immunohistochemistry.c-Jun N-terminal kinase(JNK) signal pathway inhibitor SP600125 can significantly reduce gastric mucosal injury.
Conclusion:(1) stress ulcer model is established by fluid percussing injury.(2) They had no negative correlations between PH value of gastric juice and gastric mucosal injury.But the PH value of experimental groups was obviously lower than the PH value of control group.It shows potential negative correlations between the gastric mucosal blood flow and gastric mucosa damage.(3) The expression of IL-6 near the hypothalamic paraventricular nucleus (PVN) was obvious,which may be through the paraventricular nucleus(PVN) mediated by the central cholinergic neurons excited,HPA axis,as well as the activation of 5-HT system metabolism increased stress involved in the process of stress ulceration in some pathophysiological mechanism.(4) The c-Jun N-terminal kinase(JNK) signal pathway is activated in Stress ulcer and participated in the occurrence of stress ulcer.(5) JNK signaling pathway inhibitors SP600125 reduce gastric mucosa damage of the rat in stress ulcer.As an effective means,it probably provide us a new idea of the treatment of stress ulcer.It maybe provide us very important guidelines for a new treatment strategy.
引文
1.Fisher RL,Pipkin GA,Wood JR.Stress related mucosal disease,pathophysiology,prevention and treatment.Crit Care Med,1995,11(2):323
2.Guth PH,Paulsen G.Aspirin-induced gastric injury in the rat:histologic changes and sucralfate cytoprotetion[J].Proc Soc Exp Biol Med,1987,184(4):423-428
3.Arderberg B.Prophylarxis and management of stress ulcers.Scand J Gasfroenterol 1985;20(Suppl 110):101
4.Bank S.Stress ulcers-prevention of gastrointestinal bleeding in critical care units.Med J Aust 1985;142(Suppl 3):17
5.Lucas CE,et al.Natural history and surgical dilemma of "stress" gastric bleeding.Arch Surg 1971;102:200
6.Ommaya AK,Pockoff SD,BaldwinM,et al.Experimental concuission.J,Neurosurg,1964,21:249-265
7.周伟,祝家镇.大鼠脑干机械性损伤模型的建立[J].中山医科大学学报,1997,18(1):62-64
8.Sullivan HG,Martinez J,Becker DP,et al.Fluid-percussionmodel of mechanical brain injury in the cat.J,Neurosurg,1976,45:520-534
9.Feeney DM,Boyeson MG,Linn RT,et al.Responses to corticl injury:1,Methodolodg and local effects of contusions in the rat.Brain Res,1981,211:67-77
10.Lighthall JW,Controlled cortical impact:a new experimental brain injury model.J,Neurotrauma,1988,5:1-15
11.Lighthall JW,Goshgarian HG,Pinderski CR.Characterization of axonalinjury produced by controlled cortical impact.J,Neurotrauma,1990,7:65-76
12.Lindgren S.Experimental studies of mechanical effect in head injury.Acta Shir Scand,1966;360:1-100
13.Lindgren S,Rinder L.Experimental studies in head injuries.1.Some factors influencing result of model experiments.Biophysik,1965;2:320-329
14.Lindgren S,Rinder L.Experimental studies in head injuries.2.Pressure propagation in percussion concussion.Biophysik,1966;3:174-180
15.Gennarelli TA,et al.Biological model of head injury in central nervous trauma status report.Becker DP and Povlishock,National Institute of Health,Bethesad,Maryland,1985,pp:391-423
16.Soares HD,Thomas M,et al.Development of prolonged focal edema and regional cation change of following experiment brain injury in the rat.J Neurochem,1992;58:1845-1592
17.Humber G,Sullivan,et al.J Neurosurg,1976;45:520
18.C.Edward Dixon,et al.J Neurosurg,1987;67:110
19.Yamaki T,Murakami N,Wamoto.Y,et al.Amodified fluid percussion device J,Neurotrauma,1994,11:613-622
20.Shima K,Marmarou A.Evaluation of brain-stem dysfunction following severe fluid-percussion head injury to the cat.J,Neurosurg,1991,74:270-277
21.Edward CE,Lyeth BG,Povlishock JT,et al.A fluid percussion model of experimental brain injury in the rat.J,Neurosurg,1987,67:110-119
22.Hamn RJ,Jenkins LW,Lyeth BG,et al.The effect of age on outcome following traumatic brain injury in rats.J,Neurosurg,1991,75:916-921
23.刘信龙,等。大鼠脑伤后神经行为和记忆功能障碍的实验研究,中华神经外科杂志,1994:11:307
24.李力仙,等。大液压打击法复制分级颅脑损伤的研究,中华实验外科杂志,1999;16(3):278
25.Kitagawa H,et al.Effects of water immersion stress on gastric secretion and mucosal blood flow in rats.Gastroenterology 1979;77:298
26.Garrick T,et al.Cimetidine and ranitidine protect against cold restraint-induced ulceration in rat by suppressing gastric acid secretion.Dig Dis Sci 1987;32:1261
27.Pruitt BA,et al.Stress ulcer disease in the burned patient.World J Surg 1981;5(2):209
28.Michael R,et al.A prospective study of omeprazole suspension to prevent clinically significant gastrointestinal bleeding from stress ulcer in mechanically ventilated trauma patients.J Trauma,1998;44(3):527-533
29.Shirazi SS,et al.Canine gastric acid secretion and blood flow measurement(?)hemorrhagic shock.Gaastroenterology,1977;73:75-78
30.MacLellan DG,et al.Role of vaga hyperactivity in gastric stress ulceration after acute injury to the cervical cord.Surg Gynecol Obstet 1988;166:441
31.Cho CH,Qui BS,Bruce IC.Vagal hyperactivity in stress in-duced gastric ulceration in rats[J].J Gastroenterol Hepatol,1996,11(2):125-128.
32.Thomas A.Milier.Mechanisms of stress-related mucosal damage.Am Med 1987;83(6A):8-14
133.吴蔚然。应激性溃疡。中华外科杂志1984:22(7):434-440
34.Matsumoto J,et alRole of capsaicin-sensitive afference neurons in mucosal blood flow response of rat stomach induced by mild irritants.Digestive Disease and Sciences 1992;37:1336
35.Thomas A.Milier.Mechanisms of stress-related mucosal damage.Am Med 1987;83(6A):8-14
36.Silen Wet al.The pathophysiology of stress ulcer disease.World J Surg 1981;5:165-174
37.Cheuny LY Pathophysiology of stress-induced gastric mucosal erosion:an update.Surg Gasteroenterology 1984;1:235-242
38.Robert A,et al.Stress ulcer.In selyes guide to stress research Vol 2-H selye(ed).New York:Scientific and Academic Editions 1983;22-46
39.Yabana et al.Stress-induced vascular damage and ulcer.Dig Dis and Sci 1988;33(6):751-776
40.Svanes K,et al.Role of blood flow in adaptive protection of the cat gastric mucosa.Gastroenterology 1991;100:1249-1258
41.Murakami M,et al.Pathophysiology and pathogenesis of acute gastric mucosal lesion after hypothermic restraint stress in rats.Gastroenterology,1985;88:660
42.Sakaguchi Y,et al.Gastric mucosal blood flow in onset of stress-induced ulcers-gastric mucosal blood flow,gastric wall microvascular structure and norepinephrine in the gastic wall.Ingastrointestinalfunction regulation and dieturbances.Y Kasuya,et al(ed).Amsterdam:Excerpa Medica 1983:121-138
43.解相礼,张光霁,张洪俊等。重型颅脑伤后急性胃粘膜损伤的实验研究。中华创伤杂志,1996;12(3):191-192
44.Bouma GJ.Blood pressure and intracranial pressure volume dynamics in severe head injury:relation with CBF autoregulation[J].J Neurosurg,1992;77:15
45.Menguy R.Role of gastric mucosal energy metabolism in the etiology of stress ulceration.World J Surg 1981;5:175-180
46.Cheuny LY Pathophysiology of stress-induced gastric mucosal erosion:an update.Surg Gasteroenterology 1984;1:235-242
47.Cheuny LY Gastric mucosal blood flow:its measurement and importance in mucosal defense mechanisms.J Surg Res,1984;36:282
48.Itoh M,et al.Role of oxygen-derived free radicals in hemorrhagic shock induced gastric lesions in the rat.Gastroenterology,1985;88:1162-1167
49.Del Maestro JD,et al.Free radicals as mediators of tissue injury.Acta Physiol Scand 1980;492(Supol):43-57
50.Benveniste E.1995 The role of cytokines in multiple sclerosis/autoimmune encephalitis and other neurological disorders.(In) Human Cytokines:Their Role in Research and Therapy (Agarwal B,Puri R,eds) Boston,Blackwell Science(pp) 195-216
51.McClain CJ,Cohen D,Phillips R,Ott L & Young B.(1991) Increased plasma and ventricular interleukin-6 levels in head injured patients.J Lab Clin Med 118:225-230
52.Kossmann T,Hans VHJ,ImhofHG,Stocker R,Grob P,Trentz O & Morganti-Kossmann MC.(1995) Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries.Shock 5:311-317
53.Gislason H,Rokke O,Svanes Y.Release of cytokines associated with gasrtic mucosal injury.Eur-Surg-Res.1996 Jul-Aug:28(4):278-86
54.Tatsuno I,Nishikawa T,Sasnao H,Shizawa S.Interleukin 6 Producing gastric carcinoma with fever,hypergammaglobulinemia,and Plasmacytosis in bone marrow.Gastroenterology.1994Aug,107(2):543-547
55.Hwang SL,Lieu AS,Howng SL,Hsieh JS,etal.Hypothalamic dysfunction in acute head-injured patients with stress ulcer.Kaohsiung J Med Sci.1998 Sep;14(9):554-60
56.陈钢.应激性胃溃疡.延边医学院学报.1990,13:65-69。
57.van-der-Meer-MJ,Sweep-CG,Rijnkels-CE,Pesman-GJ,Tilders-FJ Kloppenborg-PW,Hermus-AR.Acute stimulation of the hypothalamic-Pituitary-adrenal axis by IL-1 beta,TNF alpha and IL-6:a dose response study.J-Endocrinol-Invest.1996:19(3):175-82
58.杨红,张席锦.大鼠脑内5-羟色胺在应激性溃疡形成中的作用.生理学报1985:37:416-424
59.Jarkovska Z,Krsek M,Rosicka M,et al.Endocrine and metabolic activities of a recently isolated peptide hormone ghrelin,an endogenous ligand of the growth hormone secretagogue receptor.Endocr Regul,2004,38(2):80-86
60.O Carroll AM,Don AL,Lolait SJ.APJ receptor mRNA expression in the rat hypothalamic paraventricular nucleus:regulation by stress and glucocorticoids.J Neuroendocrinol,2003,15(11):1095-1101
61.Benarroch EE.Paraventricular nucleus,stress response,and cardiovascular disease.Clin Auton Res,2005,15(4):254-263
62.ZhangJF,Zheng F.The role of paraventricular nucleus of hypothalamus in stress ulcer formation in rats.Brain Res,1997,761(21):203-209
63.Robinson MJ,Cobb MH.Mitogen-activated protein kinase pathways.Curr Opin Cell Biol 1997;9:180-5
64.Seger R,Krebs EG.The MAPK signaling cascade.FASEB J 1995;9:726-35
65.Derijard B,Hibi M,Wu I-H,Barrett T,Su B,Deng T,Karin M,Davis RJ.JNKI:a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain.Cell 1994;76:1025-37
66. Kallunki T, Su B, Tsigelny I, Sluss H, Derijard B, Moore G, Davis R, Karin M. JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation. Genes Dev 1994; 8: 2996-3007
67. Jain J, Valge-Archer VE, Rao A. Analysis of the AP-1 sites in the IL-2 promoter. J Immunol 1992; 148: 1240-50
68. Foletta VC, Segal DH, Cohen DR. Transcriptional regulation in the immune system: all roads lead to AP-1. J Leukocyte Biol 1998; 63: 139-52
69. Finkenzeller G, Technau A, Marine D. Hypoxia-induced transcription of the vascular endothelial growth factor gene is independent of functional AP-1 transcription factor. Biochem Biophys Res Commun 1995; 208: 432-9
70. Schanke JT, Marcuzzi A, Podzorski RP, Van Ness B. An AP1 binding site upstream of the kappa immunoglobulin intron enhancer binds inducible factors and contributes to expression. Nucl Acids Res 1994; 22: 5425-32
71. von Knethen A, Callsen D, Brune B. NF-kappaB and AP-1 activation by nitric oxide attenuated apoptotic cell death in RAW 264.7 macrophages. Mol Biol Cell 1999; 10: 361-72
72. Pendas AM, Balbin M, Llano E, Jimenez MG, Lopez-Otin C. Structural analysis and promoter characterization of the human collagenase-3 gene (MMP13). Genomics 1997; 40: 222-33
73. TournierC,et al.Proc Natl Acad Sci USA, 1997;94:7337
74. Han Z, Boyle DL, Chang L, Bennett B, Karin M, Yang L, Manning AM, Firestein GS. c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J Clin Invest 2001; 108: 73-81
75. Eynott PR, Nath P, Leung SY, Adcock IM, Bennett BL, Chung KF. Allergen-induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N-terminal kinase. Br J Pharmacol 2003; 140: 1373-80. Epub: 17 November 2003
76. Jiang Y. Progress of study on the mechanism of activation of endothelial cells induced by lipopolysaccharide. Natl Med J China, 1999,79(1): 76-78
77. Kyriakis JM, Avruch J. Sounding the alarm: protein kinase cascades activated by stress and inflammation. J Biol Chem ,1996, 271 (40) : M313-24316
78. Jians Y,LiuAH , Zhao KS .The signal transduction pathways of mitogen - activated proteinkinase. J First Mil Med Univ 1999,19( 1) : 59-62
79. Jians Y, HanJH. P38 MAPK signal transduction pathway. Chin Bull Life Sci, 1999, 11(3) : 102-106
80. Yang X, etal= Cell , 1997, 89: 1067
81. Takahashi S, Fujita T, Yamamoto A. Role of nuclear factor-kappaB in gastric ulcer healing in rats. Am J Physiol Gastrointest Liver Physiol 2001; 280: G1296-304
82. Tebbutt NC, Giraud AS, Inglese M et al. Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice. Nat Med 2002.; 8: 1089-97
1 Zheng JF,Zheng F.The role of paraventricular nucleus of hypothalamus in stress ulcer formation in rats.Brain Res,1997,761(2):203-209
2 Kauffman GL.Stress,the brain,and the gastric mucosa.Am J Surg.1997 Sep;174(3):271-5
3 Okumura T,et al.Nippon Shokakibyo-Gakkai-zasshi 1990;87(6):1371
4 Henke PG.Hippocampal pathway to the amygdala and stress ulcer development.Brain Res Bull 1990;25:691
5 Weine H.Neurobiologic and psychobiologic mechanism in gastric function and ulceration.Western J Med 1985;143:207
6 张建福等。电刺激室旁核对大鼠应激性胃粘膜损伤的影响。生理学报1992:44(6):583-589
7 张建福等。侧脑室注射NE利Ach在电刺激室旁核对大鼠应激性胃粘膜损伤中的作用。中国应用生理学杂志1993:9(1):83
8 张建福等。侧脑室注射NE对大鼠应激性胃溃疡的影响。徐州医学院学报1992:12(3):210
9 Hwang SL,Lieu AS,Howng SL,Hsieh JS,etal.Hypothalamic dysfunction in acute head-injured patients with stress ulcer.Kaohsiung J Med Sci.1998 Sep;14(9):554-60
10 Bhargava Kp,Daas-M,Gupta-GP,Gupta-MB.Study of central neurotransmitters in stress-induced gasrtic ulceration in albino rats.Br-J-Pharmacol.1980:68(4):765-772
11 Hermandez DE,et al.Role of brain neurotransmitters on neurotensin-induced gastric cytoprotection.Pharmacol Biochem Behav 1985;22(4):509
12 Ray A,et al.The basolateral amygdala,dopamine and gastric stress formation in rats.Brain Res 1991;558:335
13 杨红等。大鼠脑内5-轻色胺在SU形成中的作用。生理学报1985:37(5):416
14 Gidener S,et al.The effect of acute bilateral adrenalectomy on serotonin-induced in hibition of gastric acid secretion and acute gastric nucosal injury in rats. Int J Exp Pathol 1996;77(4): 163-166
15 Tache Y, Yang H. Brain regulation of gastric acid secretion by peptides: Sites and mechanisms of action. Ann N Y Acad Sci. 1990;597:128-45
16 Gunion MW,Tache Y.Brain sites where bombesin and corticotropin releasing factor influence gastric secretions.Ann N Y Acad Sci. 1990;597:92-l 13
17 Hernandez DE. The role of brain peptides in the pathogenesis of experimental stress gastric ulcers. Ann N Y Acad Sci. 1990;597:28-35
18 Kauffman GL, Zhang L, Xing L, et al.Central neurotensin protects the mucosa by a prostaglandin-mediated mechanism and inhibits gastric acid secretion in the rat. Ann N Y Acad Sci. 1990;597:175-90
19 Lenz HJ. Mediation of gastrointestinal stress responses by corticotropin-releasing factor. Ann N Y Acad Sci. 1990;597:81-91
20 Penner SB, Smyth DD, Glavin GB. Decreased gastric acid output following neuropeptide Y administration into the lateral cerebral ventricle of conscious rats. Ann N Y Acad Sci.1990;597:43-50
21 Perston WL. The role of acid in upper gastrointestinal hemorrhage due to ulcer and stress-related mucosal damage. Aliment Pharmacol Ther. 1995;9 Suppl 1:43-6
22 Cho CH, Q uiBS, Bruce IC. Vagal hyperactivity in stress induced gastric ulceration in rats. J Gastroenterol Hepatol, 1996,11(2): 125-8
23 Kitagawa H, et al. Effects of water immersion stress on gastric secretion and mucosal blood flow in rats. Gastroenterology 1979;77:298
24 Garrick T, et al. Cimetidine and ranitidine protect against cold restraint-induced ulceration in rat by suppressing gastric acid secretion. Dig Dis Sci 1987;32:1261
25 Shirazi SS, et al. Canine gastric acid secretion and blood flow measurement in hemorrhagic shod:. Gaastroenterology, 1977;73:75-78
26 MacLellan DG, et al. Role of vaga hyperactivity in gastric stress ulceration after acute injury to the cervical cord. Surg Gynecol Obstet 1988; 166:441
27 Rossmann T, Hans VHJ, Imhof HG, Stocker R, Grob P, Trentz O & Morganti-Kossmann MC. (1995) Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries. Shock 5:311-317
28 Gislason H, Rokke O, Svanes Y. Release of cytokines associated with gasrtic mucosal injury.Eur-Surg-Res.1996 Jul-Aug:28(4):278-86
29 Green FW Jr, Kaplan MM, Curtis LE. Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology. 1978 Jan;74(1):38-43
30 Berstad A. Effect of storage on peptic activity of human gastric juice. Scand J Gastroenterol. 1970;5(6):525-7
31 Kappus H, et al. Toxic drug effects associated with oxygen metabolism: redox cycling and lioid peroxidation. Experientia 1981;37:1233-1258
32 Weiss ST. Oxygen, ischemia and inflammation. Acta Physiol Scand 1986;126(Suppl 548):7-39
33 Wadhwa SS, et al. Gastric injury induced by hemorrhage, local ischemia and oxygen radical generation. Am J Physiol 1987;253:G128
34 Kawano S ,Tsuji S. Role of mucosal blood flow:a conceptional review in gastric mucosal injury and protection. J Gastroenterol Hepatol,2000,15(S):Dl-6
35 Robert A, et al. Stress ulcer. In selyes guide to stress research Vol 2.H selye(ed). New York: Scientific and Academic Editions 1983;22-46
36 Sakaguchi Y, et al. Gastric mucosal blood flow in onset of stress-induced ulcers-gastric mucosal blood flow, gastric wall microvascular structure and norepinephrine in the gastic wall. In gastrointestinalfunction regulation and dieturbances. Y Kasuya,et al(ed). Amsterdam: Excerpa Medica 1983:121-138
37 Ephgrave KS, et al. Comparison of approaches to stress ulcer prophylaxis in hemorrhagic shock. J Surg Res 1987;43:52
38 Schiessel R, et al. Role of nutrient HC03~- in protection of amphibian gastric mucosa. Gastroenterology 1980;239:G536
39 Davenport HW. Gastric mucosal injury by fatty and acetylsalicylic acids. Gastroenterology 1964;46:245
40 Ritchie WP, et al. Influence of isoproterenol and cholestyramine on acute gastric mucosal ulcerogenesis. Gastroenterology 1977;73:62
41 Hingson JD. Effect of aspirin and related compounds on the fine structure of mouse gastric mucosa. Gastroenterology 1971 ;61:156
42 周婷婷,张峻,杨昭徐．巯基物质对大鼠颅脑外伤后的胃细胞保护作用．北京医学,2004,26(4)：232-35
43 Nishida K, OhtaY, Ishiguro I.Role of gastric mucosal constiuttive and inducible nitric oxide synthases in the development of srtess induced gasrtic mucosal lesions in rats.Biochem BioPhys Res Commun. 1994:199:147-154
44 Li DS, Livingston EH, Guth PH. Effect of elevated intracranial pressure on gastric acid secretion, mucosal blood flow and mucosal injury.Dig Dis Sci.1991 Oct;36(10):1348-52
45 Madroszkiewicz D,Thor P,Moskala M,etal.Effects of intracranial hypertension on gastric myoelectrical activity evaluated by using clinical and radiological symptoms.Neurol Neurochir Pol.2005 Jan-Feb;39(1):41-8
46 魏风,朱晟,谢华等.重型颅脑损伤合并消化道山血临床分析。Anthology of Medicine,2005,124(16):896-897
47 Chun-Hua Hang,Ji-Xin Shi,Jie-Shou Li,etal.Up-regulation of intestinal nuclear factor kappa B and intercellular adhesion molecule-1 following traumatic brain injury in rats.World J Gastroenterol,2005 February 28;11(8):1149-1154
48 Jimi E,Phillips R J,Rincon M,etal.Identification of a novel blocker of I kappa B alpha kinase that enhances cellular apoptosis and inhibits cellular invasion through suppression of NF-kappa B-regulated gene products.J Immunol.2005 Jun 1;174(11):7383-92
2.Guth PH,Paulsen G.Aspirin-induced gastric injury in the rat:histologic changes and sucralfate cytoprotetion[J].Proc Soc Exp Biol Med,1987,184(4):423-428
3.Arderberg B.Prophylarxis and management of stress ulcers.Scand J Gasfroenterol 1985;20(Suppl 110):101
4.Bank S.Stress ulcers-prevention of gastrointestinal bleeding in critical care units.Med J Aust 1985;142(Suppl 3):17
5.Lucas CE,et al.Natural history and surgical dilemma of "stress" gastric bleeding.Arch Surg 1971;102:200
6.Ommaya AK,Pockoff SD,BaldwinM,et al.Experimental concuission.J,Neurosurg,1964,21:249-265
7.周伟,祝家镇.大鼠脑干机械性损伤模型的建立[J].中山医科大学学报,1997,18(1):62-64
8.Sullivan HG,Martinez J,Becker DP,et al.Fluid-percussionmodel of mechanical brain injury in the cat.J,Neurosurg,1976,45:520-534
9.Feeney DM,Boyeson MG,Linn RT,et al.Responses to corticl injury:1,Methodolodg and local effects of contusions in the rat.Brain Res,1981,211:67-77
10.Lighthall JW,Controlled cortical impact:a new experimental brain injury model.J,Neurotrauma,1988,5:1-15
11.Lighthall JW,Goshgarian HG,Pinderski CR.Characterization of axonalinjury produced by controlled cortical impact.J,Neurotrauma,1990,7:65-76
12.Lindgren S.Experimental studies of mechanical effect in head injury.Acta Shir Scand,1966;360:1-100
13.Lindgren S,Rinder L.Experimental studies in head injuries.1.Some factors influencing result of model experiments.Biophysik,1965;2:320-329
14.Lindgren S,Rinder L.Experimental studies in head injuries.2.Pressure propagation in percussion concussion.Biophysik,1966;3:174-180
15.Gennarelli TA,et al.Biological model of head injury in central nervous trauma status report.Becker DP and Povlishock,National Institute of Health,Bethesad,Maryland,1985,pp:391-423
16.Soares HD,Thomas M,et al.Development of prolonged focal edema and regional cation change of following experiment brain injury in the rat.J Neurochem,1992;58:1845-1592
17.Humber G,Sullivan,et al.J Neurosurg,1976;45:520
18.C.Edward Dixon,et al.J Neurosurg,1987;67:110
19.Yamaki T,Murakami N,Wamoto.Y,et al.Amodified fluid percussion device J,Neurotrauma,1994,11:613-622
20.Shima K,Marmarou A.Evaluation of brain-stem dysfunction following severe fluid-percussion head injury to the cat.J,Neurosurg,1991,74:270-277
21.Edward CE,Lyeth BG,Povlishock JT,et al.A fluid percussion model of experimental brain injury in the rat.J,Neurosurg,1987,67:110-119
22.Hamn RJ,Jenkins LW,Lyeth BG,et al.The effect of age on outcome following traumatic brain injury in rats.J,Neurosurg,1991,75:916-921
23.刘信龙,等。大鼠脑伤后神经行为和记忆功能障碍的实验研究,中华神经外科杂志,1994:11:307
24.李力仙,等。大液压打击法复制分级颅脑损伤的研究,中华实验外科杂志,1999;16(3):278
25.Kitagawa H,et al.Effects of water immersion stress on gastric secretion and mucosal blood flow in rats.Gastroenterology 1979;77:298
26.Garrick T,et al.Cimetidine and ranitidine protect against cold restraint-induced ulceration in rat by suppressing gastric acid secretion.Dig Dis Sci 1987;32:1261
27.Pruitt BA,et al.Stress ulcer disease in the burned patient.World J Surg 1981;5(2):209
28.Michael R,et al.A prospective study of omeprazole suspension to prevent clinically significant gastrointestinal bleeding from stress ulcer in mechanically ventilated trauma patients.J Trauma,1998;44(3):527-533
29.Shirazi SS,et al.Canine gastric acid secretion and blood flow measurement(?)hemorrhagic shock.Gaastroenterology,1977;73:75-78
30.MacLellan DG,et al.Role of vaga hyperactivity in gastric stress ulceration after acute injury to the cervical cord.Surg Gynecol Obstet 1988;166:441
31.Cho CH,Qui BS,Bruce IC.Vagal hyperactivity in stress in-duced gastric ulceration in rats[J].J Gastroenterol Hepatol,1996,11(2):125-128.
32.Thomas A.Milier.Mechanisms of stress-related mucosal damage.Am Med 1987;83(6A):8-14
133.吴蔚然。应激性溃疡。中华外科杂志1984:22(7):434-440
34.Matsumoto J,et alRole of capsaicin-sensitive afference neurons in mucosal blood flow response of rat stomach induced by mild irritants.Digestive Disease and Sciences 1992;37:1336
35.Thomas A.Milier.Mechanisms of stress-related mucosal damage.Am Med 1987;83(6A):8-14
36.Silen Wet al.The pathophysiology of stress ulcer disease.World J Surg 1981;5:165-174
37.Cheuny LY Pathophysiology of stress-induced gastric mucosal erosion:an update.Surg Gasteroenterology 1984;1:235-242
38.Robert A,et al.Stress ulcer.In selyes guide to stress research Vol 2-H selye(ed).New York:Scientific and Academic Editions 1983;22-46
39.Yabana et al.Stress-induced vascular damage and ulcer.Dig Dis and Sci 1988;33(6):751-776
40.Svanes K,et al.Role of blood flow in adaptive protection of the cat gastric mucosa.Gastroenterology 1991;100:1249-1258
41.Murakami M,et al.Pathophysiology and pathogenesis of acute gastric mucosal lesion after hypothermic restraint stress in rats.Gastroenterology,1985;88:660
42.Sakaguchi Y,et al.Gastric mucosal blood flow in onset of stress-induced ulcers-gastric mucosal blood flow,gastric wall microvascular structure and norepinephrine in the gastic wall.Ingastrointestinalfunction regulation and dieturbances.Y Kasuya,et al(ed).Amsterdam:Excerpa Medica 1983:121-138
43.解相礼,张光霁,张洪俊等。重型颅脑伤后急性胃粘膜损伤的实验研究。中华创伤杂志,1996;12(3):191-192
44.Bouma GJ.Blood pressure and intracranial pressure volume dynamics in severe head injury:relation with CBF autoregulation[J].J Neurosurg,1992;77:15
45.Menguy R.Role of gastric mucosal energy metabolism in the etiology of stress ulceration.World J Surg 1981;5:175-180
46.Cheuny LY Pathophysiology of stress-induced gastric mucosal erosion:an update.Surg Gasteroenterology 1984;1:235-242
47.Cheuny LY Gastric mucosal blood flow:its measurement and importance in mucosal defense mechanisms.J Surg Res,1984;36:282
48.Itoh M,et al.Role of oxygen-derived free radicals in hemorrhagic shock induced gastric lesions in the rat.Gastroenterology,1985;88:1162-1167
49.Del Maestro JD,et al.Free radicals as mediators of tissue injury.Acta Physiol Scand 1980;492(Supol):43-57
50.Benveniste E.1995 The role of cytokines in multiple sclerosis/autoimmune encephalitis and other neurological disorders.(In) Human Cytokines:Their Role in Research and Therapy (Agarwal B,Puri R,eds) Boston,Blackwell Science(pp) 195-216
51.McClain CJ,Cohen D,Phillips R,Ott L & Young B.(1991) Increased plasma and ventricular interleukin-6 levels in head injured patients.J Lab Clin Med 118:225-230
52.Kossmann T,Hans VHJ,ImhofHG,Stocker R,Grob P,Trentz O & Morganti-Kossmann MC.(1995) Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries.Shock 5:311-317
53.Gislason H,Rokke O,Svanes Y.Release of cytokines associated with gasrtic mucosal injury.Eur-Surg-Res.1996 Jul-Aug:28(4):278-86
54.Tatsuno I,Nishikawa T,Sasnao H,Shizawa S.Interleukin 6 Producing gastric carcinoma with fever,hypergammaglobulinemia,and Plasmacytosis in bone marrow.Gastroenterology.1994Aug,107(2):543-547
55.Hwang SL,Lieu AS,Howng SL,Hsieh JS,etal.Hypothalamic dysfunction in acute head-injured patients with stress ulcer.Kaohsiung J Med Sci.1998 Sep;14(9):554-60
56.陈钢.应激性胃溃疡.延边医学院学报.1990,13:65-69。
57.van-der-Meer-MJ,Sweep-CG,Rijnkels-CE,Pesman-GJ,Tilders-FJ Kloppenborg-PW,Hermus-AR.Acute stimulation of the hypothalamic-Pituitary-adrenal axis by IL-1 beta,TNF alpha and IL-6:a dose response study.J-Endocrinol-Invest.1996:19(3):175-82
58.杨红,张席锦.大鼠脑内5-羟色胺在应激性溃疡形成中的作用.生理学报1985:37:416-424
59.Jarkovska Z,Krsek M,Rosicka M,et al.Endocrine and metabolic activities of a recently isolated peptide hormone ghrelin,an endogenous ligand of the growth hormone secretagogue receptor.Endocr Regul,2004,38(2):80-86
60.O Carroll AM,Don AL,Lolait SJ.APJ receptor mRNA expression in the rat hypothalamic paraventricular nucleus:regulation by stress and glucocorticoids.J Neuroendocrinol,2003,15(11):1095-1101
61.Benarroch EE.Paraventricular nucleus,stress response,and cardiovascular disease.Clin Auton Res,2005,15(4):254-263
62.ZhangJF,Zheng F.The role of paraventricular nucleus of hypothalamus in stress ulcer formation in rats.Brain Res,1997,761(21):203-209
63.Robinson MJ,Cobb MH.Mitogen-activated protein kinase pathways.Curr Opin Cell Biol 1997;9:180-5
64.Seger R,Krebs EG.The MAPK signaling cascade.FASEB J 1995;9:726-35
65.Derijard B,Hibi M,Wu I-H,Barrett T,Su B,Deng T,Karin M,Davis RJ.JNKI:a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain.Cell 1994;76:1025-37
66. Kallunki T, Su B, Tsigelny I, Sluss H, Derijard B, Moore G, Davis R, Karin M. JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation. Genes Dev 1994; 8: 2996-3007
67. Jain J, Valge-Archer VE, Rao A. Analysis of the AP-1 sites in the IL-2 promoter. J Immunol 1992; 148: 1240-50
68. Foletta VC, Segal DH, Cohen DR. Transcriptional regulation in the immune system: all roads lead to AP-1. J Leukocyte Biol 1998; 63: 139-52
69. Finkenzeller G, Technau A, Marine D. Hypoxia-induced transcription of the vascular endothelial growth factor gene is independent of functional AP-1 transcription factor. Biochem Biophys Res Commun 1995; 208: 432-9
70. Schanke JT, Marcuzzi A, Podzorski RP, Van Ness B. An AP1 binding site upstream of the kappa immunoglobulin intron enhancer binds inducible factors and contributes to expression. Nucl Acids Res 1994; 22: 5425-32
71. von Knethen A, Callsen D, Brune B. NF-kappaB and AP-1 activation by nitric oxide attenuated apoptotic cell death in RAW 264.7 macrophages. Mol Biol Cell 1999; 10: 361-72
72. Pendas AM, Balbin M, Llano E, Jimenez MG, Lopez-Otin C. Structural analysis and promoter characterization of the human collagenase-3 gene (MMP13). Genomics 1997; 40: 222-33
73. TournierC,et al.Proc Natl Acad Sci USA, 1997;94:7337
74. Han Z, Boyle DL, Chang L, Bennett B, Karin M, Yang L, Manning AM, Firestein GS. c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J Clin Invest 2001; 108: 73-81
75. Eynott PR, Nath P, Leung SY, Adcock IM, Bennett BL, Chung KF. Allergen-induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N-terminal kinase. Br J Pharmacol 2003; 140: 1373-80. Epub: 17 November 2003
76. Jiang Y. Progress of study on the mechanism of activation of endothelial cells induced by lipopolysaccharide. Natl Med J China, 1999,79(1): 76-78
77. Kyriakis JM, Avruch J. Sounding the alarm: protein kinase cascades activated by stress and inflammation. J Biol Chem ,1996, 271 (40) : M313-24316
78. Jians Y,LiuAH , Zhao KS .The signal transduction pathways of mitogen - activated proteinkinase. J First Mil Med Univ 1999,19( 1) : 59-62
79. Jians Y, HanJH. P38 MAPK signal transduction pathway. Chin Bull Life Sci, 1999, 11(3) : 102-106
80. Yang X, etal= Cell , 1997, 89: 1067
81. Takahashi S, Fujita T, Yamamoto A. Role of nuclear factor-kappaB in gastric ulcer healing in rats. Am J Physiol Gastrointest Liver Physiol 2001; 280: G1296-304
82. Tebbutt NC, Giraud AS, Inglese M et al. Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice. Nat Med 2002.; 8: 1089-97
1 Zheng JF,Zheng F.The role of paraventricular nucleus of hypothalamus in stress ulcer formation in rats.Brain Res,1997,761(2):203-209
2 Kauffman GL.Stress,the brain,and the gastric mucosa.Am J Surg.1997 Sep;174(3):271-5
3 Okumura T,et al.Nippon Shokakibyo-Gakkai-zasshi 1990;87(6):1371
4 Henke PG.Hippocampal pathway to the amygdala and stress ulcer development.Brain Res Bull 1990;25:691
5 Weine H.Neurobiologic and psychobiologic mechanism in gastric function and ulceration.Western J Med 1985;143:207
6 张建福等。电刺激室旁核对大鼠应激性胃粘膜损伤的影响。生理学报1992:44(6):583-589
7 张建福等。侧脑室注射NE利Ach在电刺激室旁核对大鼠应激性胃粘膜损伤中的作用。中国应用生理学杂志1993:9(1):83
8 张建福等。侧脑室注射NE对大鼠应激性胃溃疡的影响。徐州医学院学报1992:12(3):210
9 Hwang SL,Lieu AS,Howng SL,Hsieh JS,etal.Hypothalamic dysfunction in acute head-injured patients with stress ulcer.Kaohsiung J Med Sci.1998 Sep;14(9):554-60
10 Bhargava Kp,Daas-M,Gupta-GP,Gupta-MB.Study of central neurotransmitters in stress-induced gasrtic ulceration in albino rats.Br-J-Pharmacol.1980:68(4):765-772
11 Hermandez DE,et al.Role of brain neurotransmitters on neurotensin-induced gastric cytoprotection.Pharmacol Biochem Behav 1985;22(4):509
12 Ray A,et al.The basolateral amygdala,dopamine and gastric stress formation in rats.Brain Res 1991;558:335
13 杨红等。大鼠脑内5-轻色胺在SU形成中的作用。生理学报1985:37(5):416
14 Gidener S,et al.The effect of acute bilateral adrenalectomy on serotonin-induced in hibition of gastric acid secretion and acute gastric nucosal injury in rats. Int J Exp Pathol 1996;77(4): 163-166
15 Tache Y, Yang H. Brain regulation of gastric acid secretion by peptides: Sites and mechanisms of action. Ann N Y Acad Sci. 1990;597:128-45
16 Gunion MW,Tache Y.Brain sites where bombesin and corticotropin releasing factor influence gastric secretions.Ann N Y Acad Sci. 1990;597:92-l 13
17 Hernandez DE. The role of brain peptides in the pathogenesis of experimental stress gastric ulcers. Ann N Y Acad Sci. 1990;597:28-35
18 Kauffman GL, Zhang L, Xing L, et al.Central neurotensin protects the mucosa by a prostaglandin-mediated mechanism and inhibits gastric acid secretion in the rat. Ann N Y Acad Sci. 1990;597:175-90
19 Lenz HJ. Mediation of gastrointestinal stress responses by corticotropin-releasing factor. Ann N Y Acad Sci. 1990;597:81-91
20 Penner SB, Smyth DD, Glavin GB. Decreased gastric acid output following neuropeptide Y administration into the lateral cerebral ventricle of conscious rats. Ann N Y Acad Sci.1990;597:43-50
21 Perston WL. The role of acid in upper gastrointestinal hemorrhage due to ulcer and stress-related mucosal damage. Aliment Pharmacol Ther. 1995;9 Suppl 1:43-6
22 Cho CH, Q uiBS, Bruce IC. Vagal hyperactivity in stress induced gastric ulceration in rats. J Gastroenterol Hepatol, 1996,11(2): 125-8
23 Kitagawa H, et al. Effects of water immersion stress on gastric secretion and mucosal blood flow in rats. Gastroenterology 1979;77:298
24 Garrick T, et al. Cimetidine and ranitidine protect against cold restraint-induced ulceration in rat by suppressing gastric acid secretion. Dig Dis Sci 1987;32:1261
25 Shirazi SS, et al. Canine gastric acid secretion and blood flow measurement in hemorrhagic shod:. Gaastroenterology, 1977;73:75-78
26 MacLellan DG, et al. Role of vaga hyperactivity in gastric stress ulceration after acute injury to the cervical cord. Surg Gynecol Obstet 1988; 166:441
27 Rossmann T, Hans VHJ, Imhof HG, Stocker R, Grob P, Trentz O & Morganti-Kossmann MC. (1995) Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries. Shock 5:311-317
28 Gislason H, Rokke O, Svanes Y. Release of cytokines associated with gasrtic mucosal injury.Eur-Surg-Res.1996 Jul-Aug:28(4):278-86
29 Green FW Jr, Kaplan MM, Curtis LE. Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology. 1978 Jan;74(1):38-43
30 Berstad A. Effect of storage on peptic activity of human gastric juice. Scand J Gastroenterol. 1970;5(6):525-7
31 Kappus H, et al. Toxic drug effects associated with oxygen metabolism: redox cycling and lioid peroxidation. Experientia 1981;37:1233-1258
32 Weiss ST. Oxygen, ischemia and inflammation. Acta Physiol Scand 1986;126(Suppl 548):7-39
33 Wadhwa SS, et al. Gastric injury induced by hemorrhage, local ischemia and oxygen radical generation. Am J Physiol 1987;253:G128
34 Kawano S ,Tsuji S. Role of mucosal blood flow:a conceptional review in gastric mucosal injury and protection. J Gastroenterol Hepatol,2000,15(S):Dl-6
35 Robert A, et al. Stress ulcer. In selyes guide to stress research Vol 2.H selye(ed). New York: Scientific and Academic Editions 1983;22-46
36 Sakaguchi Y, et al. Gastric mucosal blood flow in onset of stress-induced ulcers-gastric mucosal blood flow, gastric wall microvascular structure and norepinephrine in the gastic wall. In gastrointestinalfunction regulation and dieturbances. Y Kasuya,et al(ed). Amsterdam: Excerpa Medica 1983:121-138
37 Ephgrave KS, et al. Comparison of approaches to stress ulcer prophylaxis in hemorrhagic shock. J Surg Res 1987;43:52
38 Schiessel R, et al. Role of nutrient HC03~- in protection of amphibian gastric mucosa. Gastroenterology 1980;239:G536
39 Davenport HW. Gastric mucosal injury by fatty and acetylsalicylic acids. Gastroenterology 1964;46:245
40 Ritchie WP, et al. Influence of isoproterenol and cholestyramine on acute gastric mucosal ulcerogenesis. Gastroenterology 1977;73:62
41 Hingson JD. Effect of aspirin and related compounds on the fine structure of mouse gastric mucosa. Gastroenterology 1971 ;61:156
42 周婷婷,张峻,杨昭徐．巯基物质对大鼠颅脑外伤后的胃细胞保护作用．北京医学,2004,26(4)：232-35
43 Nishida K, OhtaY, Ishiguro I.Role of gastric mucosal constiuttive and inducible nitric oxide synthases in the development of srtess induced gasrtic mucosal lesions in rats.Biochem BioPhys Res Commun. 1994:199:147-154
44 Li DS, Livingston EH, Guth PH. Effect of elevated intracranial pressure on gastric acid secretion, mucosal blood flow and mucosal injury.Dig Dis Sci.1991 Oct;36(10):1348-52
45 Madroszkiewicz D,Thor P,Moskala M,etal.Effects of intracranial hypertension on gastric myoelectrical activity evaluated by using clinical and radiological symptoms.Neurol Neurochir Pol.2005 Jan-Feb;39(1):41-8
46 魏风,朱晟,谢华等.重型颅脑损伤合并消化道山血临床分析。Anthology of Medicine,2005,124(16):896-897
47 Chun-Hua Hang,Ji-Xin Shi,Jie-Shou Li,etal.Up-regulation of intestinal nuclear factor kappa B and intercellular adhesion molecule-1 following traumatic brain injury in rats.World J Gastroenterol,2005 February 28;11(8):1149-1154
48 Jimi E,Phillips R J,Rincon M,etal.Identification of a novel blocker of I kappa B alpha kinase that enhances cellular apoptosis and inhibits cellular invasion through suppression of NF-kappa B-regulated gene products.J Immunol.2005 Jun 1;174(11):7383-92