水浸束缚应激大鼠胃壁细胞形态和泌酸功能的研究

背景:应激性溃疡(SU)是临床危重疾病的常见并发症,通常认为胃黏膜缺血是SU的主要发病机制,而胃酸则在此基础上起重要作用,但胃酸在SU发病中的确切作用尚未完全阐明.目的:研究水浸束缚应激(WRS)大鼠胃壁细胞形态和泌酸功能的变化,以进一步阐明胃酸在SU发病中的作用.方法:将15只Sprague-Dawley大鼠随机分为WRS2 h组、WRS 4 h组和正常对照组,予相应处理后测定胃液pH值,处死大鼠,评估胃黏膜溃疡指数(UI),以免疫荧光技术标记H /K -ATP酶后用激光共聚焦扫描显微镜观察壁细胞形态并进行分类和计数.分析胃液pH值与胃黏膜UI和分泌期壁细胞数之间的关系.结果:WRS 2 h组和WRS 4 h组的胃液pH值均较正常对照组显著降低(P＜0.01),两组WRS组之间则无显著差异.WRS 2 h组和WRS 4 h组的胃黏膜UI和分泌期壁细胞(网格样细胞)数均显著高于正常对照组(P＜0.01),其中WRS 4 h组显著高于WRS 2 h组(P＜0.01).正常对照组的胃液pH值与分泌期壁细胞数呈负相关(r＝-0.81,P＜0.05),WRS组的胃液pH值与胃黏膜UI和分泌期壁细胞数均呈负相关(r=-0.85,P＜0.05;r=-0.89,P＜0.05).结论:WRS大鼠的胃酸分泌与胃黏膜UI和分泌期壁细胞数呈正相关,从细胞学水平证明胃酸增高在SU的形成中起重要作用.     

精氨酸加压素参与电针对大鼠应激性胃黏膜损伤的保护作用

目的：探讨精氨酸加压素(AVP)参与电针(EA)对应激性大鼠胃黏膜损伤保护作用及机制.方法：健康SD大鼠98只,随机分为模型组、电针组、生理盐水对照组、AVP 100ng组、AVP 200ng组、AVP 300ng组和AVP-V_1受体阻断剂组.采用束缚冷应激胃黏膜损伤大鼠模型,观察孤束核微量注射AVP,AVP-V_1受体阻断剂,大鼠胃黏膜血流量(GMBF)、溃疡指数(UI)、胃液酸度的变化.结果：与模型组比较,电针组大鼠UI减少(t= 7.5201,P＜0.01),GMBF(mv)增加(t=2.9606,P＜0.05),胃液酸度降低(t=4.2090,P＜0.01). AVP 100,200,300ng组分别与生理盐水对照组比较,UI明显减少(t=2.2718,t=4.9082,t =6.0413：P＜0.05-0.01),GMBF明显增加(t= 2.6845,t=3.8269,t=4.8795；P＜0.05-P＜0.01),胃液酸度明显降低(t=3.0526,t=3.8565,t= 5.6251；P＜0.05-P＜0.01),并且表现明显的剂量-效应依赖关系(r=0.9978,r=0.9980,r= 0.9829；P＜0.05).AVP-V_1受体阻断剂组与生理盐水对照组比较UI增大(t=5.6815,P＜0.01),GMBF减少(t=2.3750,P＜0.05),胃液酸度增高(t=2.2046,P＜0.05).结论：孤束核内AVP参与了电针对大鼠应激性胃黏膜损伤保护作用过程.     

内皮素在大鼠冷束缚应激性溃疡中的作用

本研究采用大鼠冷束缚应激溃疡模型,动态检测了应激前及应激后血浆、胃粘膜组织内皮素-1(ET-1)含量、胃粘膜血流量(GMBF)及溃疡指数(UI)的变化,及内皮素转化酶抑制剂phosphora-midon对应激性溃疡时GMBF、UI的影响,旨在探讨内源性ET-1在应激性溃疡发生中的可能作用机     

应激大鼠胃黏膜氧化应激指标受褪黑素影响的研究

目的探讨褪黑素干预应激大鼠胃黏膜氧化应激指标影响的研究.方法采用浸水-束缚(WIR)应激实验复制大鼠应激性溃疡模型.应激前30 min,MT(melatonin)5、20mg·kg-1和应激组大鼠分别腹腔注射MT 5、20mg·kg-1和等体积生理盐水.应激6h后,观察各组大鼠胃黏膜病变情况,对溃疡指数(UI)进行评分,同时检测各组大鼠胃黏膜内丙二醛(MDA)含量、胃黏膜超氧化物歧化酶(SOD)活性和还原型谷胱甘肽(GSH)水平.结果WIR应激6h后,应激组大鼠胃黏膜MDA水平显著高于对照组(P＜0.01).MT 5、20mg·kg-1组较应激组MDA水平显著下降(P＜0.01),且MT 20mg·kg-1组显著低于MT 5mg·kg-1组(P＜0.01).应激组大鼠SOD、GSH活性较对照组明显降低(P＜0.01),MT 5、20mg·kg-1组较应激组SOD、GSH活性有升高趋势.比较各组UI发现,MT 5、20mg·kg-1组UI显著低于应激组(P＜0.01),其中MT 20mg·kg-1组UI显著低于MT 5mg·kg-1组(P＜0.05).结论褪黑素通过其抗氧化的作用对应激大鼠胃黏膜损伤起保护作用.     

内皮素、一氧化氮在内毒素血症大鼠胃粘膜损伤中的作用

目的研究ET-1/NO)失衡在内毒素血症胃粘膜损伤中的作用.方法实验选用Wistar大鼠30只,随机分成5组,每组6只,于0,20min腹腔分别注射如下两组药物.正常组:生理盐水+生理盐水.内毒素(LPS)组:LPS+生理盐水.特异性内皮素受体(ETAR)阻滞剂BQ-123组:LPS+BQ-123.NO前体L-精氨酸(L-Arg)组:LPS+L-Arg.一氧化氮合酶阻滞剂NG-硝基-L-精氨酸甲酯(L-NAME)组:LPS+L-NAME.于60min分别测定血浆、胃粘膜中ET-1,NO含量变化,以及胃粘膜血流(GMBF)、胃粘膜损伤面积的变化.结果 LPS组ET-1水平较正常组显著增高(P<0.05),NO,GMBF较正常组显著减少(P<0.05),溃疡指数显著增加(P<0.05).而BQ-123组GMBF较LPS组显著改善(P<0.05),溃疡指数显著降低(P<0.05).L-Arg组NO,GMBF较LPS组显著升高(P<0.05),ET-1水平则较LPS组显著降低(P<0.05),溃疡指数显著降低(P<0.05).L-NAME组NO,GMBF较LPS组显著减少(P<0.05),溃疡指数显著增加(P<0.05).结论内源性ET-1/NO失衡参与了内毒素血症时胃粘膜损伤病理过程.纠正内源性ET-1/NO失衡,通过改善胃粘膜血流(GMBF),减轻胃粘膜损伤.     

大鼠孤束核微量注射γ-氨基丁酸对电针抗应激性胃黏膜损伤的影响

[目的]探讨孤束核内γ-氨基丁酸(GABA)对电针(EA)抗应激性胃黏膜损伤的影响及机制。[方法]70只健康SD大鼠随机分为5组:单纯应激组、EA+应激组、0.85%氯化钠+EA+应激组、GABA+EA+应激组、荷苞牡丹碱+EA+应激组,每组14只。采用冷束缚法制备大鼠应激性胃溃疡模型,通过脑立体定位仪进行孤束核微量注射GABA和荷苞牡丹碱,测定各组大鼠胃黏膜溃疡指数(UI)、胃黏膜血流量(GMBF)、胃液酸度的变化。[结果]EA+应激组大鼠胃黏膜UI、胃液酸度降低,GMBF增加,与单纯应激组比较差异有统计学意义(P0.01)。预先孤束核给予GABA处理,可减弱EA抗胃黏膜损伤的作用,胃黏膜UI、胃液酸度增高,GMBF减少,与NS+EA+应激组比较差异有统计学意义(P0.01)。荷苞牡丹碱则明显加强EA对胃黏膜损伤的保护作用,胃黏膜UI、胃液酸度降低,GMBF增加,与NS+EA+应激组比较差异有统计学意义(P0.05)。[结论]GABA能削弱EA抗应激性胃黏膜损伤作用,其作用部分是通过孤束核内GABAA受体介导的。     

艾灸预处理对应激性溃疡大鼠胃黏膜HSP70蛋白及mRNA表达的影响

目的:观察艾灸足三里和梁门穴预处理对应激性溃疡大鼠胃黏膜热休克蛋白70(HSP70)及其基因表达的影响,探讨艾灸足阳明经穴保护胃黏膜的作用机制.方法:将60只大鼠完全随机分为空白组(A)、模型组(B)、艾灸足三里等穴组(C)和对照组(D)4组,采用水浸-束缚应激法(WRS)制备应激性溃疡模型.按Guth法计算胃黏膜损伤指数(UI),用免疫组织化学法、逆转录聚合酶链式反应(RT-PCR)法和放射免疫法分别检测处理后大鼠胃黏膜HSP70,HSP70mRNA的表达和内皮素(ET)、前列腺素E2(PGE2)的含量.结果:SU大鼠胃黏膜损伤指数B组与A、C组(P=0.000,P=0.001),D组与A、C组(P=0.001)有显著性差异,艾灸足三里等穴可使SU大鼠胃黏膜损伤指数明显下降.胃黏膜PGE2含量A组与B、D组比较差异显著(P=0.011,P=0.028),C组与B、D组比较差异显著(P=0.020,P=0.048),经艾灸预处理的大鼠胃黏膜PGE2含量均有不同程度升高.ET含量B组与A组之间有显著差异(P=0.040),经艾灸预处理的大鼠ET含量下降显著,B组与C组相比差异显著(P=0.020).造模后胃黏膜的HSP70蛋白和mRNA表达均有不同程度的增强,B组与A组相比有显著性差异(P=0.039,P=0.008);经艾灸预处理后HSP70蛋白和mRNA显著增强,C组与B、D组比较有统计学意义(蛋白:P=0.003,P=0.035;mRNA:P=0.000,P=0.001).结论:艾灸足三里、梁门穴能通过增强HSP70的蛋白和基因表达,达到对胃黏膜的保护作用,并有一定的穴位特异性.     

大鼠运动应激性胃溃疡模型的建立以及苦苣总黄酮的预防作用

背景:近年运动应激性胃溃疡受到广泛关注,有研究证实苦苣总黄酮有抗炎、抗氧化作用。目的:建立快速、稳定、可重复的大鼠运动应激性胃溃疡模型,并探讨苦苣总黄酮对运动应激性胃溃疡的干预作用。方法:100只Wistar大鼠随机分为安静对照组、1 h无负荷运动组、1 h负荷运动组、2 h无负荷运动组和2 h负荷运动组,每组20只,雌雄各半。采用游泳方式建立大鼠运动应激性胃溃疡模型,观察胃黏膜溃疡指数(UI)和病理学改变。40只雄性Wistar大鼠随机分空白对照组、1 h负荷运动模型组、大剂量苦苣总黄酮组(生药3.2 g/kg)和小剂量苦苣总黄酮组(生药1.6 g/kg),观察胃黏膜病理学改变,检测胃黏膜SOD以及胃黏膜和血清MDA含量。结果:与1 h负荷运动组相比,1 h无负荷运动组UI显著降低(P<0.01),2 h负荷运动组显著升高(P<0.01),2 h无负荷运动组无明显差异(P>0.05)。1 h、2 h无负荷运动组和1 h负荷运动组雄性大鼠UI明显高于雌性大鼠(P<0.05)。与空白对照组相比,1 h负荷运动后大鼠胃黏膜SOD含量明显降低(P<0.01),胃黏膜和血清中MDA含量明显上升(P<0.05),大剂量苦苣总黄酮可明显改善上述指标(P<0.05)。结论:1 h负荷游泳运动可有效快速地建立大鼠运动应激性胃溃疡模型。大剂量苦苣总黄酮对运动引起的大鼠应激性胃溃疡有明显预防作用。     

血管紧张素Ⅱ拮抗剂在大鼠应激性溃疡中的作用

目的:探讨血管紧张素Ⅱ拮抗剂在大鼠应激性溃疡(SU)中的作用.方法:水浸束缚应激后,肉眼计算胃黏膜溃疡指数(UI);取动脉血和胃液做血气分析计算胃黏膜内pH值;采用放射免疫方法检测血栓素B2(TXB2)和6-酮前列腺素F1α(6-K);观察胃组织病理形态学变化.结果:管紧张素Ⅱ拮抗剂组与阴性对照组比较,pH值、6-K水平显著升高(4.82±0.31vs4.53±0.11,P=0.026;974.95±109.11ng/Lvs654.50±221.31ng/L,P<0.01),而TXB2,UI显著降低(48.53±8.26ng/Lvs98.18±39.24ng/L,P<0.01;36.13±6.49vs69.00±33.27,P<0.01).病理形态学观察,血栓形成减少.血管紧张素Ⅱ拮抗剂组与奥美拉唑组比较,除6-K(974.95±109.11ng/Lvs737.61±96.10ng/L,P<0.05)外,其他数据无统计学差异.结论:血管紧张素Ⅱ拮抗剂通过舒张血管,增加胃黏膜血流量起到保护胃黏膜的作用,其机制可能是减轻肾上腺髓质对应激的反应,抑制由应激引起的儿茶酚胺的合成和释放,促进前列腺素的分泌.     

褪黑激素对应激性溃疡大鼠胃黏膜诱生型一氧化氮合酶表达的影响

背景胃黏膜诱生型一氧化氮合酶(iNOS)的过度表达在应激性溃疡的发生中起重要作用。目的研究褪黑激素(MT)对水浸鄄束缚应激大鼠胃黏膜iNOS表达的影响及其对胃黏膜的保护作用,以进一步阐明MT的作用机制。方法正常对照组不予水浸鄄束缚应激和MT预防,模型组和MT低剂量预防组、MT高剂量预防组于应激前30min分别腹腔注射含1%二甲基亚砜(DMSO)或MT5mg/kg、20mg/kg的等体积生理盐水。应激6h后处死动物,检测各组大鼠胃黏膜一氧化氮(NO)水平、iNOS蛋白和iNOSmRNA的表达,并评估胃黏膜损伤程度。结果水浸鄄束缚应激6h后,大鼠胃黏膜NO水平、iNOS蛋白和iNOSmRNA表达显著增加,胃黏膜病变明显。MT预防组大鼠胃黏膜NO水平、iNOS蛋白和iNOSmRNA表达均显著低于模型组(P<0.01),且溃疡指数(UI)显著下降(P<0.01)。MT高剂量预防组大鼠各检测指标均显著低于MT低剂量预防组(P<0.05),作用呈剂量依赖性。结论MT可预防水浸鄄束缚应激诱导的大鼠胃黏膜损伤,其机制可能与其抑制胃黏膜iNOS过度表达有关。     

Influence of NG‐nitro‐L‐arginine methyl ester and L‐arginine on gastric mucosal tolerant cytoprotection under stress

OBJECTIVE : To determine the role of endogenous nitric oxide (NO) in gastric mucosal tolerant cytoprotection under stress and its possible mechanism. METHODS : Sprague–Dawley rats were exposed to repeated water immersion and restraint stress (WRS), during which N^G‐nitro‐L ‐arginine methyl ester (L ‐NAME), a non‐selective NO synthase inhibitor, and L ‐arginine (L ‐Arg), a substrate for NO synthesis, were administered to inhibit or promote the synthesis of endogenous NO, respectively. Gastric mucosal blood flow (GMBF) was measured with an LDF‐3 Flowmeter (Electronic Instrument Factory of Nankai University, Tianjin, China), the NO level in the gastric mucosa was monitored by the Griess reaction and gastric mucosal lesions were evaluated using the ulcer index (UI). The relationships between changes in GMBF, UI and NO content in the gastric mucosa were analyzed by linear correlation analysis. RESULTS : Repeated WRS induced gastric mucosal tolerant cytoprotection and this was accompanied by increased GMBF and NO levels in the gastric mucosa. Inhibition of endogenous NO synthesis by L ‐NAME worsened mucosal lesions induced by single WRS and, after repeated WRS, the adaptive incremence in GMBF was abolished and the NO content in the gastric mucosa was significantly reduced. In contrast, enhancement of endogenous NO synthesis by L ‐Arg attenuated mucosal erosions caused by single WRS. After repeated WRS, GMBF and the NO content in the mucosa increased gradually. Mucosal lesions were negligible after rats were exposed to the fourth WRS. CONCLUSIONS : During the tolerant cytoprotection, GMBF, UI and the NO content showed regular changes and there were good relationships between them. L ‐NAME and L ‐Arg changed the levels of endogenous NO, which, accordingly, affected GMBF and the gastric tolerance. By regulating GMBF, endogenous NO may play an important role in the gastric mucosal tolerant cytoprotection under stress. Inhibition of the synthesis of NO delayed the induction of tolerant cytoprotection, whereas increased NO synthesis promoted cytoprotection.     

Role of TFF in healing of stress-induced gastric lesions

AIM: To determine the changes of pS2 and ITF of TFF expression in gastric mucosa and the effect on ulcer healing of pS2, ITF to Water-immersion and restraint stress (WRS)in rats.METHODS: Wistar rats were exposed to single or repeated WRS for 4 h every other day for up to 6 days. Gastric mucosal blood flow (GMBF) was measured by LDF-3 flowmeter and the extent of gastric mucosal lesions were evaluated grossly and histologically. Expression of pS2 and ITF mRNA was determined by RT-PCR. Immunohistochemistry was used to further detect the expression of pS2 and ITF.RESULTS: WRS applied once produced numerous gastric mucosal erosions, but the number of these lesions gradually declined and GMBF restored at 2, 4, 8 h after stress. The area of gastric mucosal lesion was reduced by 64.9 % and GMBF was increased by 89.8 % at 8 h. The healing of stress-induced ulcerations was accompanied by increased expression of pS2 (0.51±0.14 vs0.77±0.11, P＜0.01) and ITF (0.022±0.001 vs 0.177±0.010, P＜0.01). The results were demonstrated further by immunohistochemistry of pS2(0.95±0.11 vs1.41±0.04, P＜0.01) and ITF (0.134±0.001 vs 0.253±0.01,P＜0.01). With repeated WRS, adaptation to this WRS developed, the area of gastric mucosal lesions was reduced by 22.0 % after four consecutive WRS. This adaptation to WRS was accompanied by increased GMBF (being increased by 94.2 %), active cell proliferation in the neck region of gastric glands, and increased expression of pS2 (0.37±0.02 vs 0.77±0.01, P＜0.01) and ITF (0.040±0.001 vs0.372±0.010, P＜0.01). The result was demonstrated further by immunohistochemistry of pS2 (0.55±0.04 vs 2.46±0.08, P＜0.01) and ITF (0.134±0.001 vs0.354±0.070,P＜0.01).CONCLUSION: TFF may not only participate in the early phase of epithelial repair known as restitution(maked by increased cell migration),but also play an important role in the subsequent, protracted phase of glandular renewal(made by cell proliferation).     

Protective effect of omeprazole on gastric mucosal of cirrhotic portal hypertension rats

Objective:To observe the protective effect of omeprazole on gastric mucosal of cirrhotic portal hypertension rats.Methods:All rats were randomly divided into normal control group,cirrhosis and treatment group.Thioacetamide was used to establish rat model of cirrhotic portal hypertension.The necrotic tissue of gastric mucosa ulcer focus,degree of neutrophils infiltration at the ulcer margin,portal pressure,portal venous flow,abdominal aortic pressure,abdominal aortic blood flow at front end,gastric mucosal blood flow(GMBF),glycoprotein(GP)of gastric mucosa,basal acid secretion,H' back-diffusion,gastric mucosal damage index,NO,prostaglandin E_2(PGE_2) and tumor necrosis factor-α(TNF-α) were determined respectively,and the pathological changes of gastric mucosa were also observed by microscope.Results:Compared with cirrhosis group and the control group,the ulcer bottom necrotic material,gastric neutrophil infiltration and UI of the treatment group were all decreased significantly(P0.01),GMBF value,GP values,serum NO,PGE_2,TNF- a were all significantly increased.Conclusions:Omeprazole has an important protective effect on gastric mucosal and it can increase gastric mucosal blood flow and related to many factors.     

Preventive effects of geranylgeranylacetone on rat ethanol-induced gastritis

AIM: To establish a rat ethanol gastritis model, we evaluated the effects of ethanol on gastric mucosa and studied the preventive effects of geranylgeranylacetone on ethanol-induced chronic gastritis.METHODS: One hundred male Sprague-Dawley rats were randomly divided into 4 equal groups: normal control group, undergoing gastric perfusion of normal saline (NS) by gastrogavage; model control group and 2 model therapy groups that underwent gastric perfusion with ethanol (distillate spirits with 56% ethanol content) by gastrogavage for 4 wk. Low or high doses of geranylgeranylacetone were added 1 h before ethanol perfusion in the 2 model therapy groups, while the same amount of NS, instead of geranylgeranylacetone was used in that model control group. The rats were then sacrificed and stomachs were removed. The injury level of the gastric mucosa was observed by light and electron microscopy, and the levels of prostaglandin 2 (PGE₂), endothelin-1 (ET-1) and nitric oxide (NO) were measured by radioimmunoassay and the Griess method.RESULTS: The gastric mucosal epidermal damage score (EDS; 4.5) and ulcer index (UI; 12.0) of the model control group were significantly higher than that of the normal control group (0 and 0 respectively, all P = 0.000). The gastric mucosal EDS and UI of the 2 model therapy groups (EDS: 2.5 and 2.0; UI: 3.5 and 3.0) were significantly lower than that of the model control group (all P < 0.01). There was no statistically significant difference between the low-dose and high-dose model therapy groups. The expression value of plasma ET-1 of the model control group was higher than that of the normal control group (P < 0.01) and the 2 model therapy groups (all P < 0.01). The expression values of gastric mucosal PGE₂ and serum NO of the model control group were lower than those of the normal control group (all P < 0.05) and the 2 model therapy groups (all P < 0.05). The thickness of the gastric mucous layerand the hexosamine content in the model control group were significantly lower than that in the normal control group (all P < 0.01) and the 2 model therapy groups (all P < 0.05). Scanning and transmission electron microscopy observation showed that in the model control group, the epithelial junctions were vague, the intercellular joints disappeared and damage of the intracellular organelles were significantly worse than those in the normal control group. However, in the 2 model therapy groups, damage to the intercellular joints and organelles was ameliorate relative to the model control group.CONCLUSION: Administration of geranylgeranylacetone was correlated with a more favorable pattern of gastric mucosa damage after ethanol perfusion. The mechanism could be related to regulation of ET-1, NO and PGE₂.     

左旋精氨酸甲酯及左旋精氨酸对应激状态下胃黏膜耐受性细胞保护作用的影响

目的：探讨内源性一氧化氮（NO）在应激状态下胃黏膜耐受性细胞保护中的作用及其可能的机制。方法：以重复浸水束缚应激（WRS）制作动物模型,以左旋精氨酸甲酯（L－NAME）或左旋精氨酸（L－Arg）抑制或促进内源性NO的合成,动态检测胃黏膜血流量（GMBF）、溃疡指数（UI）、黏膜一化氮含量的变化。结果：重复应激后,实验对照组大鼠UI明显下降,同时GMBF上升,黏膜内NO含量增高;L－NAME使WWRS引起的胃黏膜损伤加重,消除了GMBF的递增趋势,黏膜NO含量下降;而L－Arg可减轻WRS造成的黏膜损伤,GMBF、黏膜NO含量增相应增加;GMBF、UI、黏膜NO含量变化之间有相关关系。结论：内源性NO通过调节GMBF而介导耐受性细胞保护作用,L－NAME抑制其合成,延缓这一作用,L－Arg增加其合成,促进该作用。     

Are humoral factors involved in the colonic mucosal lesion in portal hypertensive rats?

AIMS: With a prehepatic portal hypertensive rat model, we explored the involvement of humoral factors to the occurrence of portal hypertensive colopathy (PHC), another clinical entity besides portal hypertensive gastropathy (PHG) in portal hypertension, by investigating the expression of inducible nitric oxide synthase (iNOS), endothelial constitutive NOS (ecNOS), endothelin-1 (ET-1), tumour necrosis factor alpha (TNF-alpha) and vascular endothelial growth factor (VEGF) in the colonic and gastric mucosa. METHODS: Portal hypertension was produced by a two-stage ligation of portal vein plus ligation of the left adrenal vein in male Sprague-Dawley rats. Two weeks after complete obstruction of the portal vein, the portal pressure was measured and the expression of iNOS, ecNOS, ET-1, TNF-alpha and VEGF in the colonic and gastric mucosa were detected by RT-PCR and immunohistochemistry methods. RESULTS: A 1.8 fold (P < 0.01) elevation of the portal pressure was detected in the portal hypertensive rats as compared to control. Significantly up-regulation of the mRNA levels of iNOS (P < 0.01), ET-1 (P < 0.05) and TNF-alpha (P < 0.01), but not ecNOS and VEGF, were detected in the colonic mucosa of portal hypertensive rats compared with control. The mRNA of iNOS, ecNOS, ET-1, TNF-alpha and VEGF were all significantly increased at varied levels in the gastric mucosa as compared to control (P all < 0.05). No difference of the appearance and localization of immunostaining of iNOS, ecNOS, ET-1, TNF-alpha and VEGF in the colonic and gastric mucosa were seen between two groups. CONCLUSIONS: These data suggest the involvement of the upregulation of iNOS, ET-1 and TNF-alpha in the colonic mucosal lesion of portal hypertensive rats.     

Epalrestat prevents the decrease in gastric mucosal blood flow and protects the gastric mucosa in streptozotocin diabetic rats

We have recently reported that steady-state gastric mucosal blood flow (GMBF) is decreased in streptozotocin (STZ) diabetic rats, and that their GMBF response to burn-stress is impaired, probably via a nitric oxide (NO)-mediated mechanism. Accordingly, this study was designed to investigate the relation of aldose reductase (AR) and NO synthase to the regulation of GMBF during chronic hyperglycemia. STZ rats were treated with or without chronic oral administration of an AR inhibitor, epalrestat (EPA) and/or an NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME). GMBF was measured by laser-Doppler velocimetry (LDV). In the STZ rats, GMBF after a 24-h fasting period was decreased significantly 4 weeks after the onset of diabetes and this was accompanied by an increase in the gastric ulcer index (UI) (a measure of the length of gastric erosions and ulcers). Chronic oral administration of EPA to the STZ rats dose-dependently inhibited the increased UI and the decreased GMBF after the fasting stress, whereas chronic oral administration of L-NAME further increased the UI and further decreased the GMBF. EPA administered in combination with L-NAME to the STZ rats reduced the effects of L-NAME, but the effects did not reach significance. These results suggest that EPA protects the gastric mucosa of diabetic rats, by preventing the decrease in GMBF that is, at least in part, caused by NO-related mechanisms. (Received Mar. 3, 1998; accepted Aug. 28, 1998)