奥美拉唑对大鼠胃粘膜保护作用的研究

目的：探讨奥美拉唑对大鼠胃粘膜的保护作用。方法：在乙醇诱导大鼠胃粘膜损伤前，预先给予奥美拉唑、L－硝基－精氨酸甲酯（L－NAME）静脉注射。测定胃粘膜血流量（GMBF）、胃液pH和胃粘膜NO2^-/NO3^-含量，并观察胃粘膜损伤指数（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，奥美拉唑组大鼠UI明显降低（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，奥美拉唑保护胃粘膜损伤的作用明显减弱。静脉注射奥美拉唑，可增加GMBF和胃粘NO2^-/NO3^－含量，L－NAME可逆转这种作用，但对奥美拉唑抑制酸分泌作用无明显影响。结论：奥美拉唑对大鼠胃粘膜具有重要的保护作用，一氧化氮介导了这种作用。     

大鼠迷走神经背核在电针保护胃粘膜损伤中的作用

研究了大鼠迷走神经背核（DMV）在调节胃功能和影响电针保护胃粘膜损伤中的作用。电损毁DMV组与假手术组和掼毁其他脑组织组（网状巨细胞核）比较，可降低胃粘膜血流量和跨膜电位差，在应激后更加剧（P＜0．01）。损毁DMV后能基本消除电针对胃粘膜损伤的保护作用。结果提示，中枢迷走通路，特别是DMV在调整胃功能和影响电针的保护效应中起重要作用。     

大鼠迷走神经背核在电针保护胃粘膜损伤中的作用

研究了大鼠迷走神经背核（ＤＭＶ）在调节胃功能和影响电针保护胃粘膜损伤中的作用，电损毁ＤＭＶ组与假手术组和损毁其他脑组织组（网状巨细胞核）比较，可降低胃粘膜充量和跨膜电位差，在庆激后理加剧。损毁ＤＭＶ后能基本消除电针对胃粘膜损伤的保护作用，结果提示，中枢迷走通路，特别是ＤＭＶ在调整胃功能和影响电针的保护效应中直重要作用。     

非甾体类抗炎药胃粘膜损伤及预防实验研究

目的了解并比较不同非甾体类抗炎药(NSAID)对胃粘膜的损害及其机制,观察临床常用药物西咪替丁(泰胃美)、铝碳酸镁(胃达喜)及硫糖铝(舒克菲)对NSAID性胃粘膜损害的预防保护作用.方法分别以萘丁美酮(瑞力芬)、吲哚美辛(消炎痛)、乙酰水杨酸(阿斯匹林)复制大鼠NSAID性胃粘膜损伤模型(n=8),以光镜和扫描电镜观察损伤及预防应用西咪替丁、铝碳酸镁及硫糖铝后胃粘膜形态学改变,同时测定胃粘膜血流(GMBF),6-酮-前列环素F1α(6-kto-PGF1α),血栓素B2(TXB2)水平.结果吲哚美辛和乙酰水杨酸引起明显胃粘膜损害,平均损伤指数(LI)分别为2.13±0.46,2.06±0.71,萘丁美酮组胃粘膜损害则轻微(LI=0.38±0.52,P＜0.01).预防用药后吲哚美辛所致胃粘膜损害减轻(LI分别为1.04±0.76,1.12±0.35和0.98±0.57,与吲哚美辛组相比P＜0.01),GMBF增加(分别为2.89±0.80,3.07±0.33,3.43±0.49,与吲哚美辛组相比显著增加,P＜0.01),6-keto-PGF1α,TXB2抑制减弱.结论细胞保护性前列腺素合成抑制为NSAID性胃粘膜损伤的主要机制.萘丁美酮作为新型NSAID,有着较高的胃肠道安全性.     

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：观察内皮素－1（ET－1）、一氧化氮（NO）在内毒素血症胃粘膜扣伤中的作用。方法：应用内毒素血症胃粘膜损伤模型分别观察血浆、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：内毒素血症时ET－1含量增加、NO含量减少,特异性内皮素受体ETAR阻滞剂（BQ123）、NO前体L－精氨酸（L－Arg）能减轻内毒素血症时胃粘膜损伤的程度。一氧化氮合酶阻滞剂N^G－硝基－L－精氨酸甲酯（L－NAME）加重了该模型胃粘膜的损伤。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,通过改善了GMBF,减轻胃粘膜损伤。     

电针足阳明经穴对胃粘膜损伤大鼠胃粘膜血流量及生长抑素的影响

目的 :观察电针足阳明经“四白”、“天枢”、“足三里”穴对胃粘膜损伤大鼠胃窦和延髓内生长抑素(SS)含量的影响及与胃粘膜损伤、胃粘膜血流量的关系 ,以探讨经脉 -脏腑相关的物质基础。方法 :健康 SD大鼠 6 0只 ,随机分为正常对照组 (对照组 ) ,模型组 ,针刺四白组、天枢组及非穴点组共 6组 ,以乙醇灌胃造成胃粘膜损伤大鼠模型 ,观察电针大鼠足三里、天枢、四白穴对胃粘膜血流量 (氢气清除法 )的影响 ,用放免分析法检测大鼠胃窦及延髓 SS含量。结果 :胃粘膜血流量在胃粘膜损伤后明显降低 ,针刺四白、天枢、足三里及非穴点后 ,均有不同程度升高 ,尤以足三里和四白组升高明显 (P<0 .0 1) ;胃窦及延髓 SS模型组较对照组升高 (P<0 .0 5 ,<0 .0 1) ,而针刺四白、足三里组升高不明显 (P>0 .0 5 )。结论 :胃窦、延髓 SS含量变化与胃粘膜血流量的改变有一定关系 ,电针足阳明经四白、足三里穴可能通过对胃窦及延髓 SS含量的改变来影响胃粘膜血流量 ,促进胃粘膜损伤的修复。     

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.     

胃痛灵对大鼠胃粘膜血流量及脾虚大鼠模型的影响

为深入探讨胃癌灵保护胃粘膜的作用机制，研究了胃痛灵（WTL）对无水乙醇损伤大鼠胃粘膜血流量（GMBF）、脾虚大鼠D-木糖吸收率、胃壁结合粘液量以及胃酸分泌和胃蛋白酶活性的影响。结果显示WTL能够明显增加大鼠GMBF（P＜0．05）、胃壁结合粘液量（P＜0．05），提高脾虚大鼠D-木糖吸收率（P＜0．05），增强胃粘膜防御机能，但对脾虚大鼠胃酸的分泌和胃蛋白酶活性均无明显影响。在体外也无中和胃酸的能力。     

胃康胶囊对消炎痛诱导大鼠胃粘膜损伤血液中相关细胞因子含量的影响

目的：观察胃康胶囊对消炎痛引起的大鼠急性胃粘膜损伤时血液中相关细胞因子[前列腺环素（PGI2）、血小板活化因子（PAG）、肿瘤坏死因子－α（TNF-α）、表皮生长因子（EGF）]含量的影响，探讨其在保护胃粘膜损伤过程中的分子机制。方法：Wistar大鼠30只灌胃给药1周后，用消炎痛复制成急性胃粘膜损伤模型，5h后处死大鼠进行以上血液相关细胞因子的检测。结果：胃康胶囊能降低急性胃粘膜损伤大鼠血液中PAF、TNF-α的含量，升高PGI2，EGF的含量，对抗胃酸分泌增加，结论：胃康胶囊对消炎痛引起的大鼠胃粘膜损伤有保护作用。对胃溃疡有预防作用。     

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.     

Role of dorsal motor nucleus of vagus in gastric function and mucosal damage induced by ethanol in rats

Experimental evidence indicates that the autonomic nervous system, especially the cholinergic pathway, modulates the mucosal defensive mechanism and affects mucosal damage in the stomach. The present study investigated the role of the dorsal motor nucleus of vagus (DMV) in gastric function and its influences on ethanol-induced mucosal damage in pentobarbitone-anesthetized rats. Electrolytic lesion of the DMV as compared with sham operation and lesions of other brain areas, eg, nucleus reticular gigantocellularis and cuneate nucleus, reduced the basal gastric mucosal blood flow (GMBF) and also the blood flow after ethanol administration. The same operation did not affect the acid secretion either in the basal state or during the ethanol treatment period. Lesions at the caudal half of the DMV produced a bigger depression of GMBF when compared with lesion at the rostral half. In the sham-operated rats, ethanol induced severe hemorrhagic lesions in the gastric glandular mucosa, and this was significantly potentiated by lesions at the DMV, especially in the caudal half. The present findings indicate that acute DMV damage at the caudal half markedly affects the GMBF but not the acid secretion. The action on GMBF may contribute to the aggravation of ethanol-induced gastric damage in rats. These data reinforce the idea that the central vagal pathway, especially the caudal half of the DMV, plays a significant role in the modulation of GMBF, which in turn affects the integrity of gastric mucosal barrier.     

Increased susceptibility of rat gastric mucosa to ulcerogenic stimulation with aging

We examined the influences of aging on gastric damage and gastric mucosal blood flow (GMBF) responses induced by acid back-diffusion, following the barrier disruption, and investigated the relation of capsaicin-sensitive sensory nerves to these changes. Male Fischer rats 3, 13, and 24 months old were used. Under urethane anesthesia, a rat stomach was mounted on a chamber, and gastric potential difference (PD), luminal H⁺ loss, and GMBF were measured before, during, and after exposure to 20 mM sodium taurocholate (TC) for 30 min, in the presence of 50 mM HCl. Mucosal exposure to TC caused surface cell damage, PD reduction, and acid back-diffusion (luminal H⁺ loss) in all groups of rats; PD reduction and the amount of H⁺ loss were not significantly different between young and aged rats. In young rats, a marked increase of GMBF was observed with luminal acid loss following TC treatment, yet it resulted in less damage in the gastric mucosa. In aged rats, however, such GMBF responses were apparently mitigated, leading to a significant worsening of gastric mucosal lesions induced by TC. Mucosal application of capsaicin (0.1 mg/ml) caused an increase of GMBF in young rats, but this response was significantly attenuated in aged rats. In addition, the amount of calcitonin gene-related peptide (CGRP) released in the isolated stomach in response to capsaicin (1 × 10^–5 M) was significantly lower in aged animals when compared to young rats. These findings suggest that the gastric mucosa of aged rats is more vulnerable to acid back-diffusion following the barrier disruption, partly because of dysfunction of GMBF responses mediated by capsaicin-sensitive sensory neurons in the acidic conditions.     

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.     

Prostaglandin E receptor EP1 subtype but not prostacyclin IP receptor involved in mucosal blood flow response of mouse stomachs following barrier disruption

AIM: We investigated the role of prostacyclin IP receptors in gastric mucosal protection as well as functional responses induced by taurocholate Na (TC) as a mild irritant using IP receptor knockout mice, in comparison with prostaglandin (PG) E receptor EP1 subtype knockout animals. METHODS: Male C57/BL6 mice fasted for 18 h were used under urethane anesthesia. The stomach mounted on an ex vivo chamber was perfused with 20 mM HCl, and the transmucosal potential difference (PD), luminal acid loss, and gastric blood flow (GMBF) were simultaneously measured before and after exposure of the stomach to 20 mM TC for 20 min. RESULTS: Mucosal exposure to TC in wild-type mice caused a marked decrease in PD, followed by an increase in H(+) loss and GMBF. The PD gradually normalized after removal of TC from the chamber, with minimal damage in the mucosa 1 h later. The increase of GMBF following TC treatment was inhibited by indomethacin with no change in PD reduction or H(+) loss, resulting in severe lesions in the mucosa. None of these responses induced by TC were significantly altered in IP receptor knockout mice. However, in mice lacking EP1 receptors, TC did not increase GMBF, despite causing PD reduction and acid loss, and resulted in severe damage in the mucosa. Mucosal PGE(2) levels were significantly increased after TC, similarly, in all groups of mice, while levels of 6-keto-PGF(1alpha) showed a slight but not significant increase in all groups. CONCLUSION: We confirmed the importance of endogenous PGs and EP1 receptors in the adaptive protection and functional responses induced by a mild irritant in mouse stomach and further suggested that IP receptors are not actively involved in maintaining the gastric mucosal integrity under adverse conditions.     

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。     

老年胃溃疡患者粘膜血流量和粘膜电位的变化

胃粘膜血流量(GMBF)在消化性溃疡的发生、发展和愈合过程中起着重要作用,胃粘膜电位(GMPD)为检测胃粘膜结构完整性的指标。我们于1988年1～6月对40例各期老年胃溃疡患者的GMBF和GMPD进行了检测,现报告如下。病例选择与方法一、病例选择 (一)老年胃溃疡组共40例,其中男性30例,女性10例,年龄60～75岁,平均64.5     

Portal hypertension

The time-course effects of portal hypertension on gastric secretory function, mucosal blood flow, vascular permeability, and ethanol-induced gastric mucosal damage were examined in anesthetized rats. Partial ligation of the portal vein effectively produced portal hypertension one to three days later but the raised pressure returned to normal on the sixth day after ligation. This time-course effect coincided with reduced pepsin secretion and mucosal blood flow and also with potentiated ethanol-induced mucosal damage during the first to third days. These effects started to tail off on the sixth day. However, gastric acid output was significantly reduced on the third day, and this was strongest on the sixth day after operation. Portal vein ligation also reduced basal vascular permeability, which was markedly potentiated after ethanol treatment. It is concluded that: (1) portal vein blood pressure changes are a time-dependent process following ligation; (2) changes in gastric mucosal blood flow (GMBF) and lesion formation are closely related to portal hypertension; (3) gastric mucosal injury is associated with vascular damage, as evidenced by increased in vascular permeability; and (4) pepsin but not acid secretion is closely related to the state of the GMBF.     

Role of capsaicin-sensitive afferent neurons in mucosal blood flow response of rat stomach induced by mild irritants

The role of capsaicin-sensitive sensory nerves in gastric mucosal blood flow (GMBF) responses to mild irritants was investigated in the rat stomach mounted on a lucite chamber using hypertonic NaCl and 0.2 N HCl. Exposure of the mucosa to hypertonic NaCl (0.5, 0.75, 1 M) for 10 min caused a reduction in the transmucosal potential difference (PD) in a concentration-related manner, followed by an increase of luminal pH and GMBF. In contrast, mucosal application of 0.2 N HCl caused no or little change in PD and pH, but increased GMBF significantly. Functional ablation of capsaicin-sensitive sensory nerves significantly inhibited the increase of GMBF after exposure to these irritants, although the PD and pH responses induced by 1 M NaCl remained unaltered by this treatment. Pretreatment with indomethacin (5 mg/kg, subcutaneously) significantly attenuated the GMBF responses to 1 M NaCl and 0.2 N HCl and inhibited the increase of pH caused by 1 M NaCl. Mucosal application of capsaicin (0.1 mg/ml for 10 min) produced an increase of GMBF without being accompanied by change in PH and pH, and this effect was significantly blocked by either indomethacin or chemical deafferentation. These results suggest that capsaicin-sensitive sensory nerves as well as endogenous prostaglandins may be involved in the mechanism of GMBF responses induced by mild irritants, and the latter might sensitize these nerves to mucosal irritation. PD reduction may be obligatory for pH but not GMBF responses.     

The influence of acute or chronic nicotine treatment on ethanol-induced gastric mucosal damage in rats

The influences of acute or chronic nicotine pretreatment on ethanol-induced changes on gastric secretion, mucosal blood flow (GMBF), and glandular mucosal damage were studied in anesthetized rats. Ethanol administration decreased gastric acid secretion and GMBF, which were accompanied by a marked increase in gastric mucosal damage. Acute nicotine incubation 2 or 4 mg dose-dependently elevated both the titratable acid in the luminal solution and the gastric secretory volume; it also prevented the depressive action on GMBF and gastric mucosal damage in ethanol-treated animals. Chronic nicotine treatment for 10 days reduced the inhibitory action of ethanol on gastric acid secretion; the higher dose (25 micrograms/ml drinking water) potentiated the decrease of GMBF and the ulcerogenic property of ethanol. However, chronic treatment with the lower dose (5 micrograms/ml drinking water) had the opposite effects; it also markedly increased the gastric secretory volume. It is concluded that acute nicotine pretreatment elevates, whereas chronic nicotine pretreatment differentially affects GMBF. These effects could account for their protective or preventive actions on ethanol ulceration. The increase in nonacid gastric secretory volume by nicotine could partially explain its antiulcer effect. Furthermore, the acid secretory state of the stomach appears unrelated to the ulcerogenic property of ethanol.