Nebivolol prevents indomethacin-induced gastric ulcer in rats

Gastric ulcer is a very common gastrointestinal disease that may lead to dangerous complications and even death. This study was conducted to evaluate the prophylactic effect of nebivolol against indomethacin [INDO]-induced gastric ulcer. Male Wistar rats were divided into four groups: normal control, ulcer control (INDO only), omeprazole before INDO and nebivolol before INDO. Each rat to receive nebivolol and omeprazole was given the agent orally (by gavage) daily for 10 days prior to induction of ulcer by oral dosing with INDO. Four hours after INDO treatment, all rats were euthanized and their stomachs obtained for measures of gastric acidity, oxidative stress and inflammatory markers, as well as cytoprotective mediators. The results showed that a single oral dose of INDO (100?mg/kg) induced gastric acidity, an ulcer index of 2900 and significantly increased levels of gastric tumor necrosis factor (TNF)-α and malondialdehyde (MDA) and significantly decreased levels of gastric prostaglandin E₂ (PGE₂), glutathione (GSH) and nitric oxide (NO), compared to in normal control counterpart stomachs. Giving nebivolol before INDO corrected the gastric acidity and resulted in a significant increase in GSH, PGE₂ and NO and a significant decrease in TNFα and MDA gastric levels, compared to ulcer control values. Results obtained with nebivolol were comparable to those with omeprazole; the preventive index in the nebivolol group was 90.7% compared to 94.5% in rats in the omeprazole group. These studies showed that nebivolol provided a valuable role in preventing gastric ulcers induced by INDO and provided a promise for potentially protecting hypertensive patients from experiencing gastric ulcer. Thus, it is possible that, pending further studies, nebivolol could be used for pre-exposure prophylaxis from gastric ulcer in these patients.     

Gastroprotective effect of zinc sulfate in ethanol-induced ulcerogenesis in rats

In a rat model of ethanol-induced peptic ulcer it is demonstrated that pretreatment with zinc sulfate (intragastral administration) lowers the ethanol-induced damage to the gastral mucosa in a dose-dependent manner. Subcutaneous injection of indomethacin has no appreciable effect on the gastroprotective effect of zinc. It is assumed that the gastroprotective effect of zinc sulfate is not mediated by the release of endogenous prostaglandins. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 1, pp. 49–50, January, 1995 Presented by Yu. A. Romanov, Member of the Russian Academy of Medical Sciences     

Effects of misoprostol and taurine on monochloramine ulcerogenesis in rats

We compared gastroprotective characteristics of synthetic prostaglandin E₁ misoprostol and amino acid taurine on rat model of monochloramine injury to the gastric mucosa. Both substances exhibited a pronounced gastroprotective effect. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 3, pp. 309–311, March, 2006     

Role of neutrophils in indomethacin-induced gastric mucosal lesions in rats

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause clinically important gastric damage by several mechanisms. In order to evaluate the role of neutrophil infiltration in lesion formation, tissue myeloperoxidase activities were assessed in different gastric layers of the stomach both in rats with normal neutrophil levels and in neutropenic rats. Sprague-Dawley rats were treated either with indomethacin (Indo; 25 mg/kg, s.c.) or the vehicle. A group of rats were made neutropenic by administration of methotrexate (MTX; 2.5 mg/kg i.p.) once a day for 3 days. The stomachs were removed for the determination of lesion index, glutathione, lipid peroxide levels, protein oxidation and tissue myeloperoxidase activities. MTX treatment appeared to reduce neutrophil infiltration significantly while producing insignificant effects on eosinophils and macrophages. Indo administration caused multiple gastric lesions and treatment with MTX significantly reduced lesion index. In rats treated with Indo, neither glutathione nor LP levels showed any significant changes but the protein oxidation was significantly higher than that of other groups. The MPO level of gastric mucosa was increased in Indo-treated rats and reversed by MTX pretreatment. The results of the present study indicate that neutrophil infiltration in the gastric mucosa of rats may be involved in the pathogenesis of NSAID-induced gastric mucosal injury, but no correlation was found between lesion formation and protein oxidation in the gastric mucosa.     

Immunomodulatory effect of candesartan on indomethacin-induced gastric ulcer in rats

Non steroidal anti-inflammatory drugs (NSAIDs) induce gastric mucosal lesions in part by induction of oxidative stress as well as the activation of inflammatory cells and the production of proinflammatory cytokines. In this study, we examined the protective effect of candesartan (2 and 5?mg/kg) on indomethacin-induced gastric mucosa damage. Pretreatment with candesartan for 10 days reduced significantly the ulcer index induced by indomethacin injection. The preventive index of 2?mg/kg (76.74%) was higher than that of 5?mg/kg (65.11%). Both doses of candesartan were able to reduce significantly the stomach malondialdehyde content compared to indomethacin-treated group. Myeloperoxidase, tumor necrosis factor-α, cytokine-induced neutrophil chemoattractant gastric levels were significantly reduced by 2?mg/kg of candesartan more than 5?mg/kg. The Th1 cytokine interferon γ was also significantly reduced by both doses of candesartan compared to indomethacin injected group. On the other hand, indomethacin significant decreased the anti-inflammatory cytokine IL-10 gastric level. Pretreatment with candesartan (2 and 5?mg/kg) reversed this effect. In conclusion, the present study indicates that pretreatment with candesartan, can protect against the stomach injury induced by indomethacin through its antioxidant and immunomodulatory effects.     

纳布啡抑制瑞芬太尼诱导的大鼠痛觉过敏

目的研究纳布啡预处理对瑞芬太尼诱发痛觉过敏反应的影响及其可能的机制。方法将大鼠随机分为对照组、瑞芬太尼组(R组)、切口痛模型组(M组)、瑞芬太尼+切口痛模型组(RM组)及纳布啡预处理组(N+RM组)。R组、RM组和N+RM组静脉输注瑞芬太尼1.0μg(/kg·min),M组、RM组和N+RM组施足底切口术建立切口痛模型,N+RM组于瑞芬太尼输注前静脉注射纳布啡0.6 mg/kg。分别于造模前24 h(T-1)、造模后2 h(T1)、6 h(T2)、24 h(T3)和48 h(T4)测定热刺激缩足潜伏期(PWL)和机械刺激缩足阈值(PWT)。用蛋白免疫印迹法检测造模后48 h脊髓组织NR1、NR2A、NR2B、ERK1/2和p-ERK1/2的表达水平。结果与对照组相比,各组PWL和PWT均显著降低(P<0.05),NR1、NR2B和p-ERK1/2表达及p-ERK/ERK升高(P<0.05);与M组相比,RM组PWL和PWT均显著降低(P<0.05),NR1、NR2B和p-ERK1/2表达及p-ERK/ERK升高(P<0.05);与RM组相比,N+RM组PWL和PWT升高(P<0.05),NR1、NR2B和p-ERK1/2表达及p-ERK/ERK显著降低(P<0.05)。结论纳布啡可拮抗瑞芬太尼诱导的大鼠痛觉过敏。     

Possible mechanism underlying the effect of Semax on the formation of indomethacin-induced ulcers in rats

Intraperitoneal injection of Semax (synthetic analogue of ACTH4-7, MEHFPGP) in a dose of 50 mg/kg produced a protective effect on rats with experimental indomethacin-induced ulcers. Experiments on narcotized rats showed that Semax in the studied dose had no effect on basal blood flow in the stomach, but prevented reduction of blood flow induced by indomethacin. The antiulcer effect of Semax is probably related to improvement of blood flow in the gastric wall disturbed by indomethacin.     

GABA inhibits sexual behaviour in female rats

Ejaculation by male rats caused an abrupt and marked increase in the concentration of GABA in the cerebrospinal fluid and an equally abrupt and marked inhibition of sexual behaviour in female rats. The increase in the concentration of GABA in the cerebrospinal fluid and the inhibition of the behaviour was specifically mediated by the ejaculation of the male; sexual stimulation unaccompanied by ejaculation had no effect. The post-ejaculatory suppression of sexual receptivity in female rats was partially reversed by intracerebroventricular injection of the GABA antagonist bicuculline and the behaviour of receptive rats was inhibited by intracerebroventricular injection of the GABA agonist muscimol. Increasing the concentration of GABA in the cerebrospinal fluid by i.p. injection of the GABA transminase inhibitor gamma-vinyl GABA caused an increase of the concentration of GABA in the cerebrospinal fluid and inhibited the display of sexual receptivity. It is suggested that GABA mediates physiologically relevant inhibition of sexual behaviour in female rats.     

Galanin inhibits gut-related vagal neurons in rats

Galanin plays an important role in the regulation of food intake, energy balance, and body weight. Many galanin-positive fibers as well as galanin-positive neurons were seen in the dorsal vagal complex, suggesting that galanin produces its effects by actions involving vagal neurons. In the present experiment, we used tract-tracing and neurophysiological techniques to evaluate the origin of the galaninergic fibers and the effect of galanin on neurons in the dorsal vagal complex. Our results reveal that the nucleus of the solitary tract is the major source of the galanin terminals in the dorsal vagal complex. In vivo experiments demonstrated that galanin inhibited the majority of gut-related neurons in the dorsal motor nucleus of the vagus. In vitro experiments demonstrated that galanin inhibited the majority of stomach-projecting neurons in the dorsal motor nucleus of the vagus by suppressing spontaneous activity and/or producing a fully reversible dose-dependent membrane hyperpolarization and outward current. The galanin-induced hyperpolarization and outward current persisted after synaptic input was blocked, suggesting that galanin acts directly on receptors of neurons in the dorsal motor nucleus of the vagus. The reversal potential induced by galanin was close to the potassium ion potentials of the Nernst equation and was prevented by the potassium channel blocker tetraethylammonium, indicating that the inhibitory effect of galanin was mediated by a potassium channel. These results indicate that the dorsal motor nucleus of the vagus is inhibited by galanin derived predominantly from neurons in the nucleus of the solitary tract projecting to the dorsal motor nucleus of the vagus nerve. Galanin is one of the neurotransmitters involved in the vago-vagal reflex.     

丁香苷抑制大鼠椎间盘退变

背景:椎间盘退变是由于椎间盘内部髓核和纤维环组织发生损伤和退化导致的椎间盘结构和功能发生变化,目前尚无有效的治疗药物。目的:探讨丁香苷抑制大鼠椎间盘退变的作用。方法:取10只雄性SD大鼠,将每只大鼠的尾椎Co_(4)/Co_(5)椎间盘设为模型组、Co_(5)/Co_(6)椎间盘设为丁香苷组、Co_(6)/Co_(7)椎间盘设为对照组,对照组不进行任何处理,模型组、丁香苷组采用微型穿刺针进行纤维环全层穿刺建立椎间盘退变模型,造模后即刻,模型组、丁香苷组椎间盘分别注射2.5μL的生理盐水、丁香苷溶液(5μmol/L)。注射4周后取材,采用苏木精-伊红和番红O-固绿染色观察大鼠椎间盘退变程度,免疫组化染色分析大鼠椎间盘组织内Ⅱ型胶原、聚集蛋白聚糖及基质金属蛋白酶3,13的表达。结果与结论:①苏木精-伊红染色显示,模型组椎间盘高度降低,软骨终板变薄且有裂隙出现,纤维环结构紊乱且出现裂隙,髓核消失;丁香苷组椎间盘高度正常或略低于对照组,软骨终板退变程度较模型组轻,纤维环排列较模型组相对规整且无裂隙,髓核部分皱缩。②番红O-固绿染色显示,模型组椎间盘软骨终板出现缺损且软骨钙化层变薄,出现明显退变;丁香苷组椎间盘软骨终板结构形态有一定程度恢复。③免疫组化染色显示,与对照组比较,模型组椎间盘软骨组织内Ⅱ型胶原、聚集蛋白聚糖的表达降低(P<0.0001),基质金属蛋白酶3,13的表达升高(P<0.0001);与模型组比较,丁香苷组椎间盘软骨组织内Ⅱ型胶原、聚集蛋白聚糖的表达升高(P<0.001,P<0.0001),基质金属蛋白酶3,13的表达降低(P<0.001,P<0.0001)。④结果表明,丁香苷可通过抑制基质金属蛋白酶3,13的表达、提高Ⅱ型胶原和聚集蛋白聚糖的表达来改善椎间盘的结构和功能,预防和减缓椎间盘退变过程。     

The pathogenetic role of the serotonin-histamine-cyclic nucleotide system in ulcerogenesis

The study was dedicated to the role of serotonin in the development of experimental gastric ulcer in rats, and the role of serotonin, histamine, and purine bases in patients with peptic ulcer. The intensification of serotonin and histamine production was shown to promote the sanogenesis of persistent gastric ulcer.     

The role of polymorphonuclear leukocytes in the mechanisms of ulcerogenesis

The functional activity displayed by polymorphonuclear leukocytes (PL) of the peripheral blood and gastric mucosa, including ulcer margins, was studied in 50 rabbits with ulcer experimentally induced by the Okabe method and in 25 intact animals. The peripheral blood PLs were found to show substantially increased lysosomal cation proteins (LCP), enhanced alkaline phosphatase and decreased peroxidase activity. The changes in the gastric mucosa, particularly in its damaged area, were characterized by a marked microcirculatory bed response and formation of lymphocytic and, later on, pronounced neutrophilic infiltrates. The tissue PL therewith contained abundance of glycogen and LCP and intensively secreted granules. The maximum of these manifestations as viewed from PL coincided with the ulcer formation period (on days 2-3 of the experiment). When the ulcer had developed, the levels of LCP and glycogen in PL became lower. It was concluded that PL made an important contribution to ulcerogenesis.     

Dimethyl sulfoxide inhibits dimethylnitrosamine-induced hepatic fibrosis in rats

We studied the preventive effects of dimethyl sulfoxide (DMSO) on experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. Treatment with DMN caused a significant decrease in body and liver weight. Oral DMSO (2 ml/kg daily for 4 weeks) essentially prevented this DMN-induced body and liver weight loss with no major side effects. DMSO suppressed the induction of hepatic fibrosis, as determined by histological evaluation, and reduced hepatic hydroxyproline. It also suppressed the expression of mRNA for type I collagen in the liver. Because hepatic stellate cells (HSC) are the major cellular source of the collagen in hepatic fibrosis, we examined the effects of DMSO on collagen production in vitro using rat primary HSC culture. However, it was found that DMSO did not inhibit the collagen production in vitro. We next evaluated the effects of DMSO on tumor necrosis factor alpha (TNFalpha) and nitric oxide (NO) production by Kupffer cells, because these factors represent major activator of HSC, and because monocyte-macrophage infiltration has been implicated as being pathogenetically important for hepatic fibrosis induced by DMN. DMSO inhibited lipopolysaccharide (LPS)-induced TNFalpha and NO production, and reduced TNFalpha mRNA levels. DMSO also suppressed the LPS-induced nuclear factor kappa B activation in a murine macrophage-like cell line. These results suggest that the inhibitory effects of DMSO on hepatic fibrosis may be primarily exerted via blocking of DMN-induced inflammation. These results also implied that DMSO may be potentially useful for preventing the development of hepatic fibrosis.     

Oxytocin inhibits food and fluid intake in rats

Increasing evidence indirectly suggests a role for oxytocinergic neurons in the control of ingestive behaviors. The present study was aimed at directly investigating a possible effect of oxytocin on food and water intake in rats. Oxytocin, whether administered intracerebroventricularly (ICV) (1-10 micrograms/rat) or intraperitoneally (IP) (375-3,000 micrograms/kg) dose dependently inhibited food intake in freely feeding animals; in schedule-fed animals fasting for 21 h, oxytocin not only reduced food intake but also reduced the time spent eating and increased the latency to first meal. On the other hand, oxytocin antagonist d(CH2)5Tyr(Me)-[Orn8]-vasotocin, ICV injected at the dose of 10 micrograms/rat, increased food intake and time spent eating and reduced the latency to first meal; moreover, it completely prevented the effect of oxytocin. Water intake was studied both in freely drinking animals and in three different models of thirst (water deprivation, hypertonic saline administration, angiotensin II injection). In all cases, oxytocin dose dependently inhibited water intake, in a dose range of 0.1-10 micrograms/rat (ICV) or 93-750 micrograms/kg (IP). In the water deprivation model, ICV pretreatment with d(CH2)5Tyr(Me)-[Orn8]-vasotocin completely prevented the antidipsogenic effect of oxytocin. In conclusion, these data show that oxytocin directly inhibits food and water intake in rats, the effect being specifically mediated by brain oxytocin receptors. This may support the idea that the brain oxytocinergic system plays an important role in the regulation of ingestive behaviors.     

食欲素-B抑制大鼠脑缺血再灌注损伤

目的研究食欲素-B(orexin-B,OXB)对大鼠脑缺血再灌注的神经保护作用及其分子机制。方法制备大鼠大脑中动脉栓塞模型(MCAO),将大鼠随机分为:假手术组(control)、缺血再灌注组(I/R)、缺血再灌注+PBS组(I/R+PBS)和缺血再灌注+orexin-B组(I/R+OXB);通过神经功能评分确定模型是否成功;TTC染色法测定大鼠脑梗死体积;Western blot检测海马区食欲素受体2(OX2R)、p-AKT和p-GSK-3β蛋白表达;跳台实验检测大鼠学习与记忆。结果 I/R组海马中OX2R及p-AKT蛋白表达较对照组减少(P<0.05),p-GSK-3β蛋白表达增加(P<0.05),而I/R+OXB组上述变化明显减轻(P<0.05);I/R+OXB组脑梗死体积明显减少,I/R组潜伏期时间减少,错误次数增多(P<0.05),而I/R+OXB组上述变化显著减小(P<0.05)。结论食欲素-B抑制脑缺血再灌注损伤,可能与增强p-AKT活性、抑制p-GSK-3β活性有关。     

虫草素抑制哮喘大鼠支气管上皮细胞间充质转化

目的 考察虫草素(Cor)抑制哮喘大鼠上皮细胞间充质转化的作用机制.方法 将大鼠随机分为4组(n=10):对照组、模型(OVA)组、OVA+10 mg/kg Cor组、OVA+50 mg/kg Cor组.治疗7 d后,检测支气管肺泡灌洗液(BALF)中的细胞计数,苏木精-伊红(HE)染色评价气道炎性反应和气道重塑程度,...