应激性溃疡的发生及川芎嗪的防治效应

本实验观察了家兔创伤后胃粘膜损伤情况及川芎嗪的防治效应。发现动物创伤后胃粘膜损伤严重，出现应激性溃疡，同时血浆和胃粘膜组织中脂质过氧化物丙二醛含量增加，且胃粘膜细胞有明显的钙积聚。而应用川芎嗪防治的动物，脂质过氧化反应被明显地抑制，钙超载现象显著减轻，胃粘膜损伤轻微。提示，应激性溃疡的发生与自由基反应和细胞内钙超载有关，川芎嗪对应激性溃疡具有防治作用。     

康尔胃治疗消化性溃疡临床及实验研究

124例消化性溃疡患随机分为康尔胃治疗组70例．雷尼替丁对照组54例．疗程为6周。结果发现．康尔胃临床散与雷尼替丁相似，且康尔胃对脾胃虚寒型疗效优于脾虚胃热型。动物实验证实康尔胃对盐酸乙醇及消炎痛所致胃粘膜损伤具有明显防治作用，对应激性溃疡及醋酸性溃疡模型均有显抗溃疡作用．对幽门结扎型胃酸分泌有一定的抑制作用。     

核因子-κB信号通道介导褪黑素对大鼠应激性溃疡的保护作用

褪黑素(MT)是目前已知作用最强的内源性抗氧化剂，可显著减轻氧化应激对细胞和组织的损伤。研究表明脂质过氧化反应参与介导应激性溃疡的发生，提示MT对应激性溃疡可能具有一定的保护作用。为此，本实验将观察MT对大鼠应激性溃疡的保护作用，同时研究MT对胃黏膜核因子(NF)-κB活化的影响，以进一步阐明MT的作用机制。     

针刺对胃粘膜保护作用及其机制的研究进展

针刺对胃粘膜的保护作用已被大量的临床观察所证实;动物实验也发现针刺后应激性溃疡(stress ulcer,SU)的动物溃疡指数较非针刺治疗组有明显下降,因而证明针刺对胃粘膜具有保护作用,然而针刺对胃粘膜保护作用的机制尚未被完全阐明,它是由复杂的、多因素综合作用的结果,可涉及到胃的运动、分泌、血流、胃肠激素、氧自由基等各个方面。针刺通过调节机体的上述各个方面来增强胃粘膜的防御保护功能,减弱对胃粘膜的各种损伤作用而达到保护胃粘膜的作用,现就近年来有关针刺对胃粘膜的保护作用及其机制作一综述。     

应激性溃疡发生机制研究进展

概述应激性溃疡发生过程中机体神经内分泌、胃粘膜保护机制及损伤因素的病理生理学改变及其在应激性溃疡发病中的意义。     

丹参对实验性急性乙醇胃粘膜损伤的保护作用及其机理的研究

采用无水乙醇制备急性胃粘膜损伤模型，观察丹参水溶液对急性胃粘膜损伤的影响。大鼠分为对照组、乙醇损伤组及丹参水溶液保护组。乙醇灌胃给人，保护组给予丹参水溶液后再给乙醇。结果表明：保护组与损伤组比较，胃壁结合粘液量、胃粘膜血流量增多，ＳＯＤ、ＧＳＨ－Ｐｘ活性增高，ＬＰＯ含量降低，胃粘膜损伤指数明显减低。认为丹参水溶液对乙醇急性胃粘膜损伤有保护作用，此与其增强胃粘膜防御功能、清除氧自由基及抑制脂质过氧化反应有关。     

奥美拉唑预防老年人应激性溃疡出血临床疗效

老年人胃粘膜镜下常见粘膜小血管扭曲、玻璃样变狭窄，可使粘膜营养不良，屏障功能低下，在严重感染、创伤或脑出血等因素诱发下，较一般人群易产生应激性溃疡出血，死亡率较高。因此，临床上治疗老年原发病的同时，还应积极有效地预防应激性溃疡出血的产生。总结2000年12月至2003年3月54例严重创伤、感染或脑出血老年患者应用奥美拉唑预防应激性溃疡出血的临床资料。     

电针抗应激性胃溃疡大鼠脑组织和胃粘膜中一氧化氮合酶的变化

观察应激性胃溃疡大鼠脑组织和胃粘膜中一氧化氮合酶（NOS）活性的变化．并对电外足三里穴和阳陵泉穴NOS的变化及与胃粘膜损伤的关系作了比较。结果发现,应激性胃溃疡大鼠脑组织和胃粘膜NOS均增高，尤其是胃粘膜NOS增高非常显著（P＜0.01）；电针足三里使脑和胃NOS回降，应激前先电针更为明显，使胃溃疡损伤指数显著下降（P＜0.01）；而电针阳陵泉．与应激组相比虽也下降，但无统计学意义。提示NOS参与了电针对应激所致胃粘膜损伤的保护．这种保护作用可能与中枢和肠神经系统对胃功能的双重调节有关，同时NOS的变化与电针胃经足三里穴位特异性有一定的联系。     

电针对应激大鼠5-HT NOS及胃粘膜的影响

目的观察电针对胃粘膜损伤大鼠５ＨＴ、ＮＯＳ和ＮＯ的变化与胃粘膜的保护作用．方法用生化法测定应激性胃粘膜损伤大鼠胃窦及胃体粘膜５ＨＴ、ＮＯＳ及血清５ＨＴ、ＮＯ的含量，分析其电针后的变化，并对应激前后电针引起它们含量的变化进行了比较．结果电针使应激大鼠胃粘膜损伤指数下降（２７１±０４０→１８６±０６９，Ｐ＜００１）．电针使应激大鼠胃粘膜ＮＯＳ水平趋近正常对照组，应激前先电针比应激后电针的变化更为显著；电针使胃粘膜５ＨＴ水平回落（μｇ／ｇ湿重，６９１±３０８→４５１±１６２，Ｐ＜００１）．电针使应激大鼠血清ＮＯ水平回升（μｍｏｌ／Ｌ，５７８±１４９→７９１±１１１，Ｐ＜００５）．血清５ＨＴ及５ＨＩＡＡ含量持续增高．结论电针刺激使胃粘膜损伤大鼠ＮＯＳ和ＮＯ趋近正常，使胃粘膜增高的５ＨＴ回落，同时诱导释放ＮＯ，起到保护作用     

大豆油乳剂对胃粘膜保护作用的实验研究

实验研究大豆油乳剂治疗消化性溃疡的疗效及其作用机制。方法：采用阿司匹林、应激性溃疡、幽门结扎及慢性醋酸４种胃溃疡动物模型,对大豆油乳剂治疗胃溃疡的疗效进行了研究,其中慢性醋酸模型和幽门结扎模型选用Ｗｉｓｔａｒ雄性大鼠,应激性溃疡模型和阿司匹林模型选用昆明种雄性小鼠。同时通过对慢性醋酸模型鼠胃粘膜前列腺素Ｅ２（ＰＧＥ２）、超氧化物歧化酶（ＳＯＤ）及丙二醛（ＭＤＡ）的检测,对植物油乳剂治疗消化性溃疡的机制进行了探讨。结果：大豆油乳剂对４种溃疡动物模型均有疗效（Ｐ＜０．０１）。另外,大豆油乳剂可增加鼠胃粘膜的内源性ＰＧＥ２（Ｐ＜０．０１）,降低动物胃粘膜的ＳＯＤ活性（Ｐ＜０．０１）及ＭＤＡ含量（Ｐ＜０．０１）。结论：大豆油乳剂对实验动物的消化性溃疡疗效肯定,其机制主要与增加胃粘膜内源性ＰＧＥ２、减轻氧自由基对胃粘膜的损害有关。     

Role of active oxygen, lipid peroxidation, and antioxidants in the pathogenesis of gastric mucosal injury induced by indomethacin in rats.

The roles of active oxygen, lipid peroxidation, and the antioxidative defence mechanism in gastric mucosal injury induced by treatment with indomethacin in rats were investigated. The total area of gastric erosions and concentration of lipid peroxides in the gastric mucosa increased with time after administration of indomethacin (20 mg/kg, orally). The alpha-tocopherol:total cholesterol ratio in serum was significantly decreased and the activity of glutathione peroxidase, an important enzyme to scavenger of lipid peroxides, was inhibited by the administration of indomethacin. Treatments with superoxide dismutase and catalase inhibited the increases in gastric mucosal erosions and lipid peroxides in the gastric mucosa, and the reduction of serum alpha-tocopherol. Treatment with these scavengers did not improve the decreased glutathione peroxidase activity. These findings suggest that active oxygen species and lipid peroxidation play an important part in the pathogenesis of gastric mucosal injury induced by indomethacin, and that the decreased glutathione peroxidase activity aggravated the injury due to accelerated accumulation of hydrogen peroxide and lipid peroxides in the gastric mucosal cell.     

Effect of ursodeoxycholic acid on water immersion restraint stress ulcer of rats

Ursodeoxycholic acid (UDCA) has been used in the medical treatment of various gastrointestinal diseases. In this study, UDCA-supplemented rats were investigated to elucidate the role of UDCA in the pathogenesis of gastric mucosal lesions induced by water immersion restraint stress. In UDCA-administered rats, the increase of gastric mucosal lipid peroxide (LOP) and ulcer index after 2 hour's stress were prevented as compared with the rats fed on standard diet to serve as the control. In addition, the increase of serum and gastric mucosal catalase after the stress were also suppressed. These results suggested that antioxidant effect of UDCA on the lipid peroxidation may play a role in prevention of gastric lesions induced by water immersion restraint stress.     

热休克蛋白70系列与应激性溃疡之间的相互关系

生物细胞在受到各种理化因素刺激后,可以产生一系列的应激反应,诱导热休克蛋白(heat shock protein,HSP)表达.在众多的HSP中,HSP70家族是生物进化过程中最为保守也是目前人们研究最多的一组蛋白.应激可以诱导机体胃黏膜的损伤并可以降低胃黏膜的屏障保护作用,进而导致应激性溃疡的产生,同时加速热休克蛋白的合成,而热休克蛋白反过来又可预防应激性溃疡的发生,抑制胃黏膜细胞凋亡,促进胃溃疡的愈合.本文综述了主要的热休克蛋白分子的分类、调节以及在应激性溃疡中的表达和应用,并简要论述了通过诱导热休克蛋白表达而作为胃黏膜保护剂的几种药物.     

Duodenal ulcer

Although the etiology of duodenal ulcer is not known, its treatment with drugs that reduce acid secretion is well accepted. The central role of calcium in stimulus-secretion coupling resulting in acid secretion by gastric parietal cells is documented. However, the status of intracellular calcium in gastric parietal cells in the basal state in patients with duodenal ulcer is not known. Multiple endoscopic gastric mucosal biopsies from the corpus of the stomach of 52 patients were processed and isolated parietal cells were studied. Intracellular calcium was estimated using fura-2-acetoxymethyl ester. Influx and efflux were determined by using radioactive calcium. Acridine orange retention was used to assess acid production. Only calcium influx at 20 min was significantly (P<0.01) more in patients with duodenal ulcer as compared to the control group. There was no difference between the groups in calcium influx at 0 and 60 min; calcium efflux at 0, 20, and 60 min; intracellular free calcium and acid secretion. We conclude that in the unstimulated state calcium homeostasis in isolated parietal cells of patients with duodenal ulcer shows only a minimal difference as compared to controls.     

Effect of teprenone on acute gastric mucosal lesions induced by cold-restraint stress.

The effects of intragastric administration of teprenone on acute gastric mucosal lesions induced by cold-restraint stress was investigated using a model of obstructive jaundice. Rats received teprenone 200 mg/kg/day for a week before stress; nontreated rats served as controls. Teprenone suppressed stress-induced depressions in defensive factors (blood flow, transmucosal potential difference, hexosamine content and lectin staining of carbohydrate residues) and suppressed increases in lesion-enhancing factors (gastric mucosal lysosomal enzyme activity and thiobarbituric acid reactants showing lipid peroxidation). Intragastric pH did not change significantly with teprenone but the ulcer index decreased. These results showed that teprenone protects gastric mucosa against stress, even in the presence of obstructive jaundice.     

替米沙坦对脑出血急性应激性胃黏膜病变大鼠胃黏膜细胞增殖和凋亡的影响

目的探讨血管紧张素Ⅱ受体拮抗剂替米沙坦对脑出血急性应激性胃黏膜病变大鼠胃黏膜细胞增殖和凋亡的影响。方法健康成年SD大鼠96只,随机分为假手术组、脑出血组、替米沙坦组,每组32只,各组再分为1、2、3和5d4个时间点,每个时间点8只大鼠。制作脑出血大鼠模型,大体观察胃黏膜病变并计算溃疡指数;HE染色光镜下观察胃黏膜组织形态学改变;免疫组织化学法检测胃黏膜增殖细胞核抗原(PCNA)蛋白的表达;TUNEL检测胃黏膜凋亡细胞。结果与假手术组比较,脑出血组大鼠1、2、3和5d胃黏膜溃疡指数明显增大、PCNA表达明显减少、TUNEL凋亡细胞明显增多(P<0.01)。与脑出血组比较,替米沙坦组大鼠1、2、3和5d胃黏膜溃疡指数明显减小、PCNA表达增多、TUNEL凋亡细胞减少(P<0.05)。结论替米沙坦能够减小脑出血急性应激性胃黏膜病变大鼠胃黏膜溃疡指数、增加PCNA表达、减少TUNEL凋亡细胞,减轻应激性胃黏膜病变。     

Effects of Rebamipide, a Novel Anti-Ulcer Agent, on Gastric Mucosal Injury Induced by Platelet-Activating Factor in Rats

We examined the role of gastric mucosal bloodflow, lipid peroxidation, and neutrophil accumulationmediated by platelet-activating factor in the protectiveeffect of rebamipide against gastric mucosal injury in rats. The intravenous injection ofplatelet-activating factor induced hyperemia andhemorrhagic erosions in rat stomachs. Rebamipide did notaffect the decrease in the gastric mucosal blood flow induced by platelet-activating factor. Theincrease in gastric injury score afterplatelet-activating factor injection and the increase inthiobarbituric acid-reactive substances weresignificantly inhibited by the administration of rebamipide. Thegastric injury score was closely correlated with theaccumulation of lipid peroxides. Tissue-associatedmyeloperoxidase activity in the gastric mucosasignificantly increased after platelet activating factorinjection; this increase was not influenced byrebamipide treatment. The protective effect ofrebamipide against the platelet-activitingfactor-induced gastric mucosal injury may be due to direct inhibitionof lipid peroxidation or scavenging of oxygen radicalsthat initiate lipid peroxidation.     

创伤应激对兔胆汁流量及胃肠激素的影响

目的研究创伤应激胆汁流量、血浆胃动素、胃泌素、胰高血糖素含量的变化及其关系。方法行胆总管插管引流胆汁计量胆汁流量，将兔双下肢钳断制备应激模型，记录创伤应激前后胆汁流量的变化，同时检测血浆胃动素、胃泌素、胰高血糖素含量的改变。结果应激后兔胆汁流量较应激前明显增多，血浆内胃动素(MOT)、胃泌素(GAS)、胰高血糖素(GL)含量升高，胆汁流量的变化与激素的改变一致。结论创伤应激可使兔胆汁流量明显增多，胃肠激素的变化可能是影响胆汁分泌和排出的重要原因。应激条件下由于胃排空障碍和幽门功能紊乱，胆汁流量的增多可能加重胆汁反流，促进溃疡的发生。     

不同抗溃疡药物对应激性溃疡发生、发展过程中细胞凋亡的影响

背景：研究不同抗溃疡药物在防治应激性溃疡(SU)时，其对胃黏膜细胞学行为的作用是否有助于SU的防治。目的：观察抗溃疡药物奥美拉陛、米索前列醇和铝碳酸镁对SU的疗效，及其对细胞凋亡和与凋亡相关的细胞因子一氧化氮合酶(NOS)表达的影响。方法：水浸—束缚应激(WRS)结束后2h，计算胃黏膜损伤的溃疡指数(UI)；原位末端标记(TUNEL)法检测胃黏膜细胞凋亡；免疫组化法检测神经型NOS(nNOS)和诱导型NOS(iNOS)表达的变化。结果：奥美拉陛(0)组、米索前列醇(M)组和铝碳酸镁(H)组胃黏膜损伤均较生理盐水组显著减轻(P＜0．01)，胃黏膜细胞凋亡发生率均显著降低(P＜0．01)，但0组和M组的效果优于H组。与生理盐水组比较，3组用药组的nNOS表达均显著增加(P＜0．01)，iNOS表达均显著降低(P＜0．01)，M组和H组的nNOS表达升高较0组更为显著(P＜0．05)。结论：奥美拉唑、米索前列醇和铝碳酸镁作用于SU发生的不同环节，可显著抑制细胞凋亡的发生，对SU均有明显防治作用。寻找对细胞有直接保护作用的药物以提高细胞的抗应激能力可能是防治SU的最终途径。     

Induction and intracellular localization of a 72-kDa heat shock protein in rat gastric mucosa after water-immersion stress

We investigated the expression and changes in the intracellular localization of a 72-kDa heat shock protein (HSP72) in rat gastric pyloric and fundic mucosa before and after water-immersion stress. Severe mucosal damage was found in the fundic mucosal area of the stomach after this stress. However, no mucosal lesion developed in the pyloric mucosal area. HSP72 in both the soluble and insoluble fractions of the pyloric and the fundic mucosal areas was significantly increased after water-immersion stress, peaking 6 h after the initiation of the stress. The increase in HSP72 was more significant in the pyloric mucosal area than in the fundic mucosal area under both normal and stress conditions. The increase of HSP72 in the pyloric mucosal cells occurred prior to the formation of the mucosal lesions, whereas the increase of HSP72 in the fundic mucosal cells was observed after ulcer formation. An immunohistochemical study showed that HSP72 was constitutively expressed in the cytoplasm of the gastric mucosal cells, and that the intranuclear induction of HSP72 was remarkably intense in the pyloric mucosal cells, especially in the proliferative zone, compared with the fundic mucosal cells. Our results may suggest that HSP72 has an important cytoprotective function in gastric mucosal cells and that there is a “biophysical” difference between pyloric and the fundic mucosal cells.