前列腺素缺乏条件下促胃动力药胃复安对大鼠胃粘膜的损伤作用与可能机制

目的探讨前列腺素(prostaglandin,PG)缺乏条件下促胃动力药胃复安对大鼠胃粘膜的损伤作用与可能机制。方法 PG缺乏状态由5mg/kg吲哚美辛诱导;雄性SD大鼠随机分组:对照组;胃复安两组(30mg/kg,60mg/kg);吲哚美辛两组(5mg/kg,25mg/kg);吲哚美辛5mg/kg合用胃复安三组(10mg/kg,30mg/kg,60mg/kg);阿托品组(阿托品-吲哚美辛5mg/kg+胃复安60mg/kg),禁食24h后,生理盐水或吲哚美辛灌胃,30min后皮下注射胃复安或生理盐水,阿托品灌胃前10min皮下注射,4h后取血,处死大鼠取胃行损伤测定:放免法测血浆内皮素(Endothelin ET-1);生化法测—氧化氮(nitric oxide NO)、丙二醛(Malondialdhyde MDA)、谷胱甘肽过氧化酶(Glutathioneperoxidase GSH-Px)含量。结果吲哚美辛合用胃复安三组胃粘膜均有明显损伤,ET-1、MDA升高(p<0.05.p<0.01),NO、GSH-Px下降(p<0.05,p<0.01);吲哚美辛25ng/kg组损伤严重,ET-1、MDA升高(p<0.01),NO、GSH-Px下降(p<0.01,P<0.05);胃复安60mg/kg胃有轻微损伤,各指标无显著变化;其余各组未见明显损伤及指标变化。结论(1)PG缺乏条件下促胃动力药胃复安可引起胃黏膜出血性损伤,可能与ET-1升高、NO下降致胃黏膜微循环紊乱有关.MDA升高,GSH-Px减少可能为损伤后的继发反应结果,加剧了黏膜损伤。(32)胃动力有潜在的引起胃黏膜损伤的能力,PG缺乏增加了胃黏膜对胃高动力的敏感性。提示临床上非甾体抗炎药(NSAIDs)服用者应慎用胃动力药,因为合用可能形成或加剧胃黏膜损伤。     

Nitric oxide synthase inhibition results in immediate postoperative recovery of gastric, small intestinal and colonic motility in awake rats

Background Nitric oxide (NO) is known to inhibit gastrointestinal motility. However, no detailed analysis of gastric, small intestinal and colonic motor effects, including effects on contraction frequency, has, as yet, been reported after NO inhibition in awake rats. We therefore investigated the effects of NO synthase inhibition on gastric, small intestinal and colonic motility in awake rats under baseline conditions and in a postoperative ileus model.Methods In Sprague–Dawley rats, strain gauge transducers were sutured either to the gastric corpus, the small intestine or the colon. After 3 days, l-NMMA (NO synthase inhibitor), d-NMMA or vehicle was given i.v., while the motility was recorded continuously. In addition, postoperative gastric, small intestinal or colonic motility was investigated after l-NMMA or vehicle treatment prior to abdominal surgery. The motility index, the contraction amplitude, the area under the contraction amplitude and the contraction frequency were analysed.Results l-NMMA decreased gastric motility to 60±8% for about 15 min, but continuously increased small intestinal motility to 221±22% and colonic motility to 125±7% compared to baseline (baseline=100%; p<0.01 for all comparisons). l-NMMA increased the contraction frequency throughout the gastrointestinal tract (stomach, 13±2%; small intestine, 8±1%; colon, 16±5%; p<0.01 vs. baseline for all comparisons). l-NMMA injection prior to surgery did not prohibit intraoperative inhibition of gastrointestinal motility, but did result in immediate recovery of gastric, small intestinal and colonic motility postoperatively (l-NMMA vs. vehicle, 0–60 min postoperatively; stomach, 90±9% vs. 53±3%; small intestine, 101±5% vs. 57±3%; colon, 134±6% vs. 60±5%; p<0.01 for all comparisons; no significant difference between preoperative baseline motility and l-NMMA treated rats postoperatively).Conclusions Under baseline conditions, endogenous NO inhibits small intestinal and colonic motility and gastric, small intestinal and colonic contraction frequency in awake rats. In the early postoperative period, endogenous NO is a major inhibitory component that seems to constitute the common final pathway of mediators and the neural pathways inhibiting gastrointestinal motility in rats.     

Role of vasoactive intestinal peptide and nitric oxide in the modulation of electroacupucture on gastric motility in stressed rats

INTRODUCTION In recent years, along with the extensive research into enteric nerve system (ENS), increasing evidence shows that peptidergic neurotransmitters are the key factors regulating the gastric motility. Our previous research[1-3] showed that electroacupucture (EA) at acupoints of the Stomach Meridian of Foot-Yangmin may regulate gastric movement, increase blood flow in the microvessels in the gastric mucosa, and exert a protective effect on gastric mucosa. Nitric oxide (NO) an…     

Effects of Hyperhomocysteinemia on Non-Adrenergic Non-Cholinergic Relaxation in Isolated Rat Duodenum

The effect of hyperhomocysteinemia induced by pretreatment with methionine 12 weeks prior to the study on the responses induced by gamma-aminobutyric acid (GABA), electrical field stimulation (EFS), and ATP have been evaluated in isolated rat duodenum. In the presence of adrenergic and cholinergic blockade, EFS (60 V, 1 ms, 1-3 Hz) induced frequency-dependent relaxations of the preparation. GABA and ATP also caused submaximal relaxation of the rat duodenum. The relaxations induced by GABA, EFS, and ATP were not significantly changed in duodenal tissues from hyperhomocysteinemic rats compared with control rats. GABA- and EFS-induced relaxations were inhibited by N-nitro-L-arginine methyl ester (L-NAME; 3 x 10(-4) M) in both hyperhomocysteinemic and control rats. On the other hand, L-NAME incubation did not affect ATP-induced relaxation. These results suggest that hyperhomocysteinemia does not cause an important impairment on non-adrenergic non-cholinergic innervation of the rat duodenum.     

Glucagon-like peptide-2 modulates the nitrergic neurotransmission in strips from the mouse gastric fundus

AIM To investigate whether glucagon-like peptide-2(GLP-2) influences the neurally-induced responses in gastric strips from mice, since no data are available. METHODS For functional experiments, gastric fundal strips were mounted in organ baths containing Krebs-Henseleit solution. Mechanical responses were recorded via forcedisplacement transducers, which were coupled to a polygraph for continuous recording of isometric tension. Electrical field stimulation(EFS) was applied via two platinum wire rings through which the preparationwas threaded. The effects of GLP-2(2 and 20 nmol/L) were evaluated on the neurally-induced contractile and relaxant responses elicited by EFS. Neuronal nitric oxide synthase(n NOS) enzyme was evaluated by immunohistochemistry.RESULTS In the functional experiments, electrical field stimulation(EFS, 4-16 Hz) induced tetrodotoxin(TTX)-sensitive contractile responses, which were reduced in amplitude by GLP-2(P 0.05). In the presence of the nitric oxide(NO) synthesis inhibitor L-NNA, GLP-2 no longer influenced the neurally-evoked contractile responses(P 0.05). The direct smooth muscle response to methacholine was not influenced by GLP-2(P 0.05). In the presence of guanethidine and carbachol, the addition of GLP-2 to the bath medium evoked TTX-sensitive relaxant responses that were unaffected by L-NNA(P 0.05). EFS induced a fast NO-mediated relaxation, whose amplitude was enhanced in the presence of the hormone(P 0.05). Immunohistochemical experiments showed a significant increase(P 0.05) in n NOS immunoreactivity in the nerve structures after GLP-2 exposure. CONCLUSION The results demonstrate that in gastric fundal strips, GLP-2 influences the amplitude of neurally-induced responses through the modulation of the nitrergic neurotransmission and increases n NOS expression.     

NO参与了胃起搏调控胃慢波活动

目的观察NOS抑制剂L-NAME对胃慢波以及刺激能量的影响,旨在探讨胃起搏作用机制。方法通过手术建立Wistar大鼠胃起搏模型,随机分为4组(每组8只),分别腹腔给予不同剂量L-NAME,以生理盐水作对照。应用多导胃肠电记录仪记录胃慢波,L-NAME对胃慢波的影响应用频谱分析方法进行分析。结果大剂量(50mg/kg)注射时,L-NAME能引起胃电紊乱。正常慢波百分比明显降低(55.3%±4.0%),与对照组(91.7%±3.0%)比较,P<0.001。胃起搏仍能纠正胃电紊乱,正常慢波百分比得到改善(90.9%±2.5%),且所需的EPS较对照组明显升高(878.1±11.4vs537.5±91.6ms×mA,P<0.001)。L-NAME诱发的胃电节律失常以胃电过缓多见(41.3%±1.8%)。但给小剂量L-NAME(12.5mg/kg、25mg/kg)时,正常慢波百分比变化不明显(87.4%±4.9%、86.3%±5.6%),与对照组比较(91.7%±3.0%)差异无显著性;其慢波被控制时所需EPS分别为(487.5±64.1、550±53.5ms×mA),与对照组比较(537.5±91.6ms×mA),P>0.05。结论NOS抑制剂L-NAME能引起大鼠胃电紊乱,增大刺激能量能纠正之,表明NO可能参与了胃起搏对胃慢波活动的调控作用。     

一氧化氮在雷贝拉唑对大鼠胃黏膜损伤保护中的作用

目的:探讨一氧化氮(NO)在雷贝拉唑对大鼠胃黏膜损伤保护中的作用．方法:在乙醇诱导大鼠胃黏膜损伤前,预先给予雷贝拉唑(20 mg/kg)灌胃,1-硝基-精氨酸甲酯(1-NAME,4 mg／kg)、1-精氨酸(250 mg／kg)及d-精氨酸(250 mg／kg)iv．采用激光多普勒血流计(LDF)测定胃黏膜血流量(GMBF),采用镉粒还原和比色法测定胃黏膜和血浆NO-2／NO-3含量,并观察胃黏膜损伤指数(UI)、溃疡坏死组织和中性粒细胞浸润严重程度的变化．结果:与模型损伤组比,雷贝拉唑组大鼠UI明显降低(5．5±0．5 vs 25．2±2.3,P<0．01),溃疡坏死组织和中性粒细胞浸润程度明显减轻(坏死物质 → ／≤ :1／9 vs 8／2,P<0．01;中性粒细胞 → ／≤ :3／7 vs 9／1,P<0．01)．预先用1-NAME处理后,雷贝拉唑保护胃黏膜损伤作用明显减弱;1-NAME抑制作用可被1-精氨酸拮抗,而不被d-精氨酸拮抗．向胃内灌注雷贝拉唑,可增加GMBF、胃黏膜和血浆NO-2／NO-3,1-NAME可逆转这种作用,但对雷贝拉唑抑制酸分泌作用无明显影响．结论:雷贝拉唑对大鼠胃黏膜损伤保护作用与NO有关,而与雷贝拉唑抑制酸分泌作用无关．     

应激对大鼠胃黏液-碳酸氢盐屏障影响的实验研究

目的观察应激对大鼠胃壁结合黏液及碳酸氢盐分泌的影响,探讨应激影响胃碳酸氢盐分泌的机制。方法40只SD大鼠等分为对照组和应激1 h、2 h和4 h组,以水浸束缚方法制备应激模型,测定各组大鼠胃壁结合黏液量和黏液凝胶层厚度。另取30只SD大鼠等分为3组,A组予奥美拉唑以抑制胃酸分泌,B组予奥美拉唑和左旋硝基精氨酸甲酯,C组予奥美拉唑、L-精氨酸和左旋硝基精氨酸甲酯,采用灌注滴定法测定应激后2 h胃碳酸氢盐分泌量。结果对照组与应激1 h、2 h和4 h组胃壁结合黏液量分别是(0．137±0．03)、(0．143±0．012)、(0．066±0．016)和(0.016±0．017)吸光度／g组织;黏液凝胶层厚度分别是(71．08±5．85)、(74．50±12．85)、(57．63±6．45)和(51．35±2．84)μm。与对照组比,应激1 h组结合黏液量及凝胶层厚度差异无统计学意义(P>0．05),而应激2 h、4 h组显著低于对照组及应激1 h组(P<0．01)。3组大鼠应激状态下胃碳酸氢盐分泌速率均呈下降趋势,应激2 h内胃碳酸氢盐分泌量分别为(9.3±2．6)、(14．0±2．7)和(7．6±1．4)μmol(P<0．01)。结论应激状态下胃壁结合黏液量、黏液凝胶层厚度和胃碳酸氢盐分泌量进行性降低,提示应激后胃黏液-碳酸氢盐屏障受损,内源性一氧化氮参与介导了应激抑制胃碳酸氢盐分泌的过程。     

埃索美拉唑对胃黏膜的保护作用及其机制

目的:探讨埃索美拉唑对大鼠胃黏膜保护的作用及其机制.方法:在乙醇诱导大鼠胃黏膜损伤前,预先给予埃索美拉唑(20 mg/kg)灌胃,L-硝基-精氨酸甲酯(L-NAME,4 mg/kg)和L-精氨酸(250 mg/kg)iv.采用激光多普勒血流计(LDF)测定胃黏膜血流量(GMBF),镉粒还原和比色法测定胃黏膜和血浆NO-2/NO-3含量,并观察胃黏膜损伤指数(ulcer index,UI)、溃疡坏死组织和中性粒细胞浸润严重程度的变化.结果:与模型损伤组比,埃索美拉唑组大鼠UI明显降低(5.6±2.2 vs 25.3±2.4,P＜0.01),溃疡坏死组织和中性粒细胞浸润程度明显减轻(P＜0.01).预先用L-NAME处理后,埃索美拉唑保护胃黏膜损伤作用明显减弱;L-NAME抑制作用可被L-精氨酸拮抗.向胃内灌注埃索美拉唑,可增加GMBF、胃黏膜和血浆NO-2/NO-3,L-NAME可逆转这种作用,但对埃索美拉唑抑制酸分泌作用无明显影响.结论:埃索美拉唑通过NO介导对大鼠胃黏膜损伤有重要的保护作用,而与埃索美拉唑抑制酸分泌作用无关.     

Can adiponectin have an additional effect on the regulation of food intake by inducing gastric motor changes?

The regulation of food intake is a complex mechanism, and the hypothalamus is the main central structure implicated. In particular, the arcuate nucleus appears to be the most critical area in the integration of multiple peripheral signals.Among these signals, those originating from the white adipose tissue and the gastrointestinal tract are known to be involved in the regulation of food intake.The present paper focuses on adiponectin, an adipokine secreted by white adipose tissue, which is reported to have a role in the control of feeding by acting centrally. The recent observation that adiponectin is also able to influence gastric motility raises the question of whether this action represents an additional peripheral mechanism that concurs with the central effects of the hormone on food intake. This possibility, which represents an emerging aspect correlating the central and peripheral effects of adiponectin in the hunger-satiety cycle, is discussed in the present paper.     

一氧化氮合酶和微血管生成与胃癌发展的关系

目的　研究诱导型一氧化氮合酶 (iNOS)在人胃癌组织中的表达及其与胃癌微血管形成、淋巴结转移及临床分期的关系。方法　采用免疫组化S P法检测 50例原发性胃癌组织、癌周组织及 2 0例正常胃黏膜组织中iNOS的表达 ,同时检测微血管密度 (MVD) ,以抗CD3 4标记血管内皮细胞 ,并分析其与肿瘤行为之间的关系。结果　 50例胃癌组织中iNOS阳性表达率为 70 .0 % ,MVD均值为 2 2 .0± 9 .8,显著高于癌周组织 (16.2 % ,6.1± 3 .4)和正常胃组织 (15.0 % ,5.5± 2 .6;P <0 .0 1)。按TNM分期 ,Ⅳ期胃癌组织iNOS阳性表达率为 93 .8% ,MVD为 42 .3± 3 .7,两者显著高于Ⅰ、Ⅱ、Ⅲ期 ,差异有显著性 (P <0 .0 1)。有淋巴结转移组iNOS的阳性表达率为 84.6% ,MVD均值为 2 7.4± 6.5;无淋巴结转移组iNOS阳性表达率为 54.2 % ,MVD均值为 15.3± 4.7,两组差异有显著性 (P <0 .0 5)。iNOS阳性表达组及高MVD值 (≥ 2 2 .0 )组的 3年生存率均显著低于iNOS阴性表达组及低MVD值 (<2 2 .0 )组 ,差异有显著性 (P <0 .0 5)。结论　胃癌组织中iNOS高阳性表达 ,随着iNOS阳性表达的增强 ,MVD值也增加 ,两者呈正相关。iNOS的表达及MVD与胃癌TNM分期、淋巴结转移及预后有密切关系。iNOS的表达及MVD值可作为判断胃癌预后的重要指标     

潘托拉唑对胃黏膜损伤保护作用及其机制

目的:探讨潘托拉唑对大鼠胃黏膜损伤保护的作用及其机制.方法:在乙醇诱导大鼠胃黏膜损伤前,预先给予(iv)潘托拉唑(20mg/kg)、L-硝基-精氨酸甲酯(L-NAME,4mg/kg)及L-精氨酸(250mg/kg).采用激光多普勒血流计(LDF)测定胃黏膜血流量(GMBF),采用镉粒还原和比色法测定胃黏膜和血浆NO-2/NO-3含量,并观察了胃黏膜损伤指数(ulcerindex,UI)、溃疡坏死组织和中性粒细胞浸润严重程度的变化.结果:与模型损伤组比,潘托拉唑组大鼠UI明显降低(5.7±2.1vs25.4±2.5,P<0.01),溃疡坏死组织和中性粒细胞浸润程度明显减轻.预先用L-NAME处理后,潘托拉唑保护胃黏膜损伤作用明显减弱;L-NAME抑制作用可被L-精氨酸拮抗.iv潘托拉唑,可增加GMBF、胃黏膜和血浆NO-2/NO-3,L-NAME可逆转这种作用,但对潘托拉唑抑制酸分泌作用无明显影响.结论:潘托拉唑通过一氧化氮介导对大鼠胃黏膜损伤有重要的保护作用,而与潘托拉唑抑制酸分泌作用无关.     

The role of nitric oxide in the inhibition of gastric epithelial proliferation in portal hypertensive rats

BACKGROUND/AIM: Portal hypertension is associated with inhibition of gastric epithelial proliferation and increased gastric nitric oxide synthase activity. Whether the nitric oxide inhibits gastric epithelial proliferation is unclear. METHODS: Portal vein ligation was performed to induce portal hypertension in rats. The rats were treated for 7 days with either vehicle or N(G)-nitro-L-arginine methyl ester (L-NAME) at 5 mg/kg or 25 mg/kg doses (gastric gavage, twice a day). Sham-operated rats treated with vehicle served as controls. Hemodynamic parameters were measured using radiolabeled microspheres in anesthetized animals. Gastric epithelial proliferation was assessed by evaluating the proliferative cell nuclear antigen labeling index. RESULTS: The cardiac index and gastric fundic blood flow were higher, and the gastric fundic proliferative cell nuclear antigen labeling index was lower in the portal hypertensive rats than in the controls. In portal hypertensive rats, the 5 mg/kg dose of L-NAME decreased the cardiac index and increased the gastric fundic proliferative cell nuclear antigen labeling index to levels similar to those found in the controls, but did not affect gastric fundic blood flow significantly. The 25 mg/kg dose of L-NAME further decreased both the cardiac index and the gastric fundic blood flow, but did not affect the gastric proliferative cell nuclear antigen labeling index significantly. CONCLUSIONS: In portal hypertensive rats, the correction of systemic hyperdynamic circulation by NO inhibition is associated with normalization of gastric epithelial proliferation. Excessive nitric oxide may inhibit gastric epithelial proliferation in portal hypertension.     

The Role of the L-Arginine-Nitric Oxide Pathway for Peristalsis in the Opossum Oesophageal Body

Knudsen MA, Frøbert O, Tøttrup A. The role of the L-arginine-nitric oxide pathway for peristalsis in the opossum oesophageal body. Scand J Gastroenterol 1994;29:1083-1087.

Background: The aim of the study was to determine the effect of N^G-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide (NO) synthesis, on primary peristalsis in the oesophageal body.

Methods: Peristalsis was induced by pharyngeal stroking in 14 lightly anaesthetized opossums. Oesophageal pressures were monitored with a four-channel, perfused catheter assembly and registered with external transducers 1, 4, 7, and 10 cm proximal to the oesophagogastric junction. Propagation time was the time taken for a contraction to travel between two recording sites and was determined in the proximal, middle, and distal parts of the oesophagus (propagation time between 10 and 7 cm, 7 and 4 cm, and 4 and 1 cm recording sites, respectively).

Results: L-NNA (10^-7-10^-5mol/kg) dose-dependently reduced propagation time of the contraction in the distal oesophagus from 1.13 ± 0.24 sec to 0.27 ± 0.19 sec, whereas propagation in the proximal and middle parts of the oesophagus was unaffected. JV^G-nitro-D-arginine (D-NNA; 10^-5 mol/kg) had no influence on propagation time. In animals treated with L-NNA (10^-5 mol/kg) atropine (50 μg/kg) had no influence on propagation time in any part of the oesophagus. L-Arginine (10^-4 mol/kg) had no influence on the propagation time in animals treated with L-NNA (10^-5 mol/kg) and atropine (50 μg/kg). Neither D-NNA (10^-5 mol/kg) nor L-NNA (10^-7-10^-5 mol/kg) influenced the amplitude of the contractions at any of the recording sites. In animals given L-NNA (10^-5 mol/kg) atropine (50 μg/kg) reduced the amplitude of the contraction significantly only at the distal recording site (1-cm recording site) from 62.0 ± 4.9 mmHg to 34.5 ± 5.3 mmHg. L-Arginine (10^-4 mol/kg) had no effect on the amplitude of contractions.

Conclusion: The L-arginine-NO pathway plays a role in the control of primary peristalsic contractions of the oesophagus.     

脂联素对大鼠心肌缺血-再灌注损伤时心律失常的影响

目的：观察脂联素对大鼠心肌缺血再灌注损伤时心律失常的影响并探讨其可能机制。方法：32只8周龄雄性大鼠被随机分为假手术组、缺血一再灌注（IR）组、地尔硫卓组和脂联素（APN）组,每组8只。①假手术组：只穿线,旷置90min;②IR组：先阻断血流30min,再灌注60min;③地尔硫卓组和APN组：先阻断血流30min,于再灌注开始时,从鼠尾静脉分别注射地尔硫卓（3．5μg／g·min）、APN（60ng／g·min）．再灌注60min。以Medlab生物信号采集处理系统连续监测各组心电图的变化。各模型组于再灌注60min后处死大鼠。测定血清、心肌组织一氧化氮（NO）的含量。结果：（1）与假手术组比较,IR组再灌注60min时段里．8只大鼠均出现再灌注心律失常．再灌注过程中ST段抬高的幅度显著增高（P〈0．001）,心肌组织、血清中NO含量均明显降低（P〈0．001）;（2）与IR组比较．APN组再灌注60min时段里,没有出现再灌注心律失常,再灌注过程中ST段抬高幅度显著下降（P〈0．001）,心肌组织、血清中NO含量均明显升高（P〈0．001）,且优于地尔硫卓组（P〈0．001）。结论：脂联素对缺血一再灌注损伤造成的心律失常有一定的保护作用．其机制可能与脂联素增加心肌组织、血清中NO含量有关。     

银杏叶提取物对大鼠不同状态胃动力的影响及其机制

目的 探讨银杏叶提取物(Egb)对正常状态和冷束缚应激引起的胃肠功能紊乱的情况下大鼠胃动力的影响及可能机制.方法 采用冷束缚应激的方法建立胃肠功能紊乱模型,应用葡聚糖蓝2000(DB-2000)作为染料观察Egb在正常及应激状态对胃排空速率的影响;并利用比色法观察大鼠胃组织和血浆中一氧化氮(nitricoxide,NO)含量的变化.结果 在正常状态下,Egb对胃排空速率无显著性影响.冷束缚应激可导致大鼠胃排空减慢(P<0.05).Egb干预可明显拮抗应激引起的胃排空减慢(P<0.05).Egb对正常大鼠胃组织和血浆中NO含量没有影响;冷束缚应激可导致胃内NO含量降低(P<0.01),而血浆中NO升高(P<0.01).Egb可降低应激引起的血浆NO含量的升高(P<0.01).结论 Egb在不同状态下对大鼠胃动力的影响有所不同,具有正相调节作用.NO可能参与了Egb对大鼠胃动力的调节作用.     

Novel human and mouse genes encoding a shank-interacting protein and its upregulation in gastric fundus of W/WV mouse

BACKGROUND AND AIMS: A division of labor exists between different classes of interstitial cells of Cajal (ICC) in the gastrointestinal tract. In the stomach and small intestine, ICC at the level of the myenteric plexus (IC-MY) act as slow wave pacemaker cells, whereas intramuscular ICC (IC-IM) in the stomach act as intermediaries in enteric motor neurotransmission. The muscle layers of the gastric fundus do not have IC-MY, therefore electric slow waves are not generated. Intramuscular ICC are absent in the gastric fundus of W/WV mutant mice, and excitatory and inhibitory motor nerve responses are reduced in these tissues. The absence of IC-IM in W/WV mutants in the fundus provides a unique opportunity to study the molecular changes that are associated with the loss of these cells. METHODS: The tissue gene expression of wild-type and W/WV mice from gastric fundus was assayed using a murine microarray chip analysis displaying a total of 8734 elements. RESULTS: Twenty-one queries were differentially expressed in wild-type and W/WV mice. One candidate gene, encoding a novel protein homologous to rat Shank-interacting protein (Sharpin) was significantly upregulated in fed and starved W/WV mice. The full-length clone of the murine gene and its human counterpart were isolated and designated as Shank-interacting protein-like 1 (SIPL1). Human SIPL1 complementary DNA encodes a protein of 345 amino acids. This gene was localized to chromosome 8. SIPL1 was abundantly expressed in human stomach and small intestine, and scarcely expressed in cecum and rectum. CONCLUSIONS: Gene analysis showed that SIPL1 differentially express in the gastric fundus of normal and W/WV mice. The upregulation of SIPL1 in the fundus of W/WV mice, and expression in the upper gastrointestinal tract suggest that the SIPL1 gene could be associated with ICC function in mice and humans.     

一氧化氮和前列腺素在门静脉高压性胃病大鼠胃粘膜灌注中的作用

目的 探讨一氧化氮（NO）和前列腺素在门静脉高压性胃病（PHG）大鼠胃粘膜灌注中的作用。方法 部分结扎大鼠门静脉主干2周后,采用中性红清除率法测定大鼠胃粘膜血流量（GMBF）,同时观察门静脉压力（PVP）的变化。结果 PHG组大鼠GMBF和PVP显著高于假手术组（t=3.431、3．312,P＜0．01）。低剂量的NO合成酶抑制剂L－硝基－精氨酸甲酯（L－NAME）呈剂量依赖性降低PHG大鼠GMBF,而对假手术组GMBF无明显影响;高剂量的L－NAME（12mg/kg)能非常显著降低PHG和假手术组大鼠GMBF。前列腺素环氧合酶抑制剂消炎痛能明显降低PHG组大鼠GMBF,而对假手术组GMBF无明显影响;预先给消炎痛处理后在假手术组大鼠中,静脉注射低剂量L－NAME（4mg/kg)前后GMBF无明显变化,高剂量L－NAME（12mg/kg)降低大鼠的GMBF与未用消炎痛处理组比无明显变化;预先给消炎痛处理后在PHG组大鼠中,L－NAME剂量（4mg/kg、12mg/kg)依赖性降低大鼠的GMBF与未用消炎痛处理组比无明显改变。结论 NO、前列腺素在调节PHG大鼠的GMBF起重要作用,但两者无协同作用。     

Expression of nitric oxide synthase in human gastric carcinoma and its relation to p53, PCNA

AIM: To investigate the expression of NOS in gastric carcinoma, and to explore the relationship between the expression of nitric oxide synthases (NOS) and p53, PCNA, pathological features and clinical staging of gastric cancer. METHODS: The activity of NOS protein was investigated in 85 samples of human gastric carcinoma and 25 samples of normal gastric mucosal tissue by biochemical assay. We then examined the expression of NOS, p53, PCNA in 85 samples of human gastric cancer was examined by immunohistochemistry, and NOS mRNA expression in 85 gastric cancer tissue specimens by In situ hybridization. RESULTS: Biochemical assay showed that the activity of NOS was significantly higher in gastric carcinoma than in normal gastric mucosal tissues (t=0.4161, P＜0.01). Immunohistochemistry revealed that endothelial nitric oxide synthase (eNOS) expressed in all samples of normal gastric mucosa, but only 6 cases of 85 gastric cancer specimens showed weak positive immunohistochemical reactions to eNOS (20%). Inducible nitric oxide synthase (iNOS) was expressed strongly in human gastric carcinoma (81.2%). In situ hybridization analysis showed that iNOS mRNA expression was significantly stronger than eNOS mRNA expression in gastric cancer tissue (X~2 = 10.23, P＜0.01). The expression of iNOS in gastric cancer was associated with differentiation, clinical stages or lymph node metastases (r=0.3426,P＜0.05). However, iNOS expression did not correlate with histological classifications and morphological types. The expression of iNOS was significantly correlated with p53 or PCNA expression (r=0.3612, P＜0.05). The expression of neuronal nitric oxide synthase (nNOS) was not examined by immunohistochemistry and in situ hybridization in gastric cancer specimens and normal gastric mucosa. CONCLUSION: In human gastric cancer, there is an enhanced expression of iNOS, but not of eNOS. NOS promotes the proliferation of tumor cells and plays an important role in gastric cancer spread. Inactivation of antioncogene p53 and overexpression of iNOS might play a synergetic role in the process of carcinogenesis of human gastric carcinoma.