IGFR-I expression and structural analysis of the hard palatine mucosa in an ethanol-drinking rat strain (UChA and UChB)

The study analyzed the effects of chronic alcohol ingestion on the ultrastructure of the lining epithelium of the hard palatine mucosa of rats UChA and UChB (lines with voluntary alcohol consumption) in order to contribute to the understanding of the consequences of alcohol abuse for the morphology of the digestive system. Thirty female adult animals aged 120 days were divided into three experimental groups. (1) Ten UChA rats (genetically low ethanol consumer) with voluntary intake of 10% v/v (5.45 g/kg/day) ethanol solution and water. (2) Ten UChB (genetically high ethanol consumer) rats with voluntary intake of 10% v/v (7.16 g/kg/day) ethanol solution and water. (3) Ten Wistar rats with voluntary ad libitum water intake (control group). Both groups received Nuvital pellets ad libitum. The IGFR-I expression was intense in both experimental groups. The epithelial cells of the alcoholic rats UChA and UChB showed many alterations such as the presence of lipid droplets, altered nuclei, nuclei in corneum layer and disrupted mitochondria. It was concluded that ethanol intake induces ultrastructural lesions in the hard palatine mucosa.     

Binding of albumin promotes bacterial survival at the epithelial surface

Human serum albumin (HSA) is the dominating protein in human plasma. Many bacterial species, especially streptococci, express surface proteins that bind HSA with high specificity and affinity, but the biological consequences of these protein-protein interactions are poorly understood. Group G streptococci (GGS), carrying the HSA-binding protein G, colonize the skin and the mucosa of the upper respiratory tract, mostly without causing disease. In the case of bacterial invasion, pro-inflammatory cytokines are released that activate the epithelium to produce antibacterial peptides, in particular the chemokine MIG/CXCL9. In addition, the inflammation causes capillary leakage and extravasation of HSA and other plasma proteins, environmental changes at the epithelial surface to which the bacteria need to respond. In this study, we found that GGS adsorbed HSA from both saliva and plasma via binding to protein G and that HSA bound to protein G bound and inactivated the antibacterial MIG/CXCL9 peptide. Another surface protein of GGS, FOG, was found to mediate adherence of the bacteria to pharyngeal epithelial cells through interaction with glycosaminoglycans. This adherence was not affected by activation of the epithelium with a combination of IFN-γ and TNF-α, leading to the production of MIG/CXCL9. However, at the activated epithelial surface, adherent GGS were protected against killing by MIG/CXCL9 through protein G-dependent HSA coating. The findings identify a previously unknown bacterial survival strategy that helps to explain the evolution of HSA-binding proteins among bacterial species of the normal human microbiota.     

Kir4.1 channel expression is essential for parietal cell control of acid secretion

Kir4.1 channels were found to colocalize with the H(+)/K(+)-ATPase throughout the parietal cell (PC) acid secretory cycle. This study was undertaken to explore their functional role. Acid secretory rates, electrophysiological parameters, PC ultrastructure, and gene and protein expression were determined in gastric mucosae of 7-8-day-old Kir4.1-deficient mice and WT littermates. Kir4.1(-/-) mucosa secreted significantly more acid and initiated secretion significantly faster than WT mucosa. No change in PC number but a relative up-regulation of H(+)/K(+)-ATPase gene and protein expression (but not of other PC ion transporters) was observed. Electron microscopy revealed fully fused canalicular membranes and a lack of tubulovesicles in resting state Kir4.1(-/-) PCs, suggesting that Kir4.1 ablation may also interfere with tubulovesicle endocytosis. The role of this inward rectifier in the PC apical membrane may therefore be to balance between K(+) loss via KCNQ1/KCNE2 and K(+) reabsorption by the slow turnover of the H(+)/K(+)-ATPase, with consequences for K(+) reabsorption, inhibition of acid secretion, and membrane recycling. Our results demonstrate that Kir4.1 channels are involved in the control of acid secretion and suggest that they may also affect secretory membrane recycling.     

Lipopolysaccharide increases gastric and circulating NUCB2/nesfatin-1 concentrations in rats

Bacterial lipopolysaccharide (LPS) is an established animal model to study the innate immune response to Gram-negative bacteria mimicking symptoms of infection including reduction of food intake. LPS decreases acyl ghrelin associated with decreased concentrations of circulating ghrelin-O-acyltransferase (GOAT) likely contributing to the anorexigenic effect. We also recently described the prominent expression of the novel anorexigenic hormone, nucleobindin2 (NUCB2)/nesfatin-1 in gastric X/A-like cells co-localized with ghrelin in different pools of vesicles. To investigate whether LPS would affect gastric and circulating NUCB2/nesfatin-1 concentration, ad libitum fed rats were equipped with an intravenous (iv) catheter. LPS was injected intraperitoneally (ip, 100 μg/kg) and blood was withdrawn before and at 2, 5, 7 and 24 h post injection and processed for NUCB2/nesfatin-1 radioimmunoassay. Gastric corpus was collected to measure NUCB2 mRNA expression by RT-qPCR and NUCB2/nesfatin-1 protein concentration by Western blot. Injection of LPS increased plasma NUCB2/nesfatin-1 concentrations by 43%, 78% and 62% compared to vehicle at 2 h, 5 h and 7 h post injection respectively (p < 0.05) and returned to baseline at 24 h. The plasma NUCB2/nesfatin-1 increase at 2 h was associated with increased corpus NUCB2 mRNA expression (p < 0.01), whereas NUCB2 mRNA was not detectable in white blood cells. Likewise, gastric NUCB2 protein concentration was increased by 62% after LPS compared to vehicle (p < 0.01). These data show that gastric NUCB2 production and release are increased in response to LPS. These changes are opposite to those of ghrelin in response to LPS supporting a differential gastric regulation of NUCB2/nesfatin-1 and ghrelin expression derived from the same cell by immune challenge.     

Slitrk6 expression profile in the mouse embryo and its relationship to that of Nlrr3

Slitrk6 is a member of the Slitrk family of proteins, which are integral membrane proteins possessing two leucine-rich repeat (LRR) domains and a carboxy-terminal domain partially similar to that in the trk neurotrophin receptor proteins. Here, I show that Slitrk6 is uniquely expressed in various organs, different from other Slitrk genes which are predominantly expressed in neural tissues. In the developing mouse embryo, Slitrk6 expression was detected in the otic cyst, lateral trunk epidermis and its underlying mesenchymal tissue, limb bud, maxillary process, pharyngeal arches, cochlea, retina, tongue, tooth primordium, central nervous system (CNS), and the visceral organ primordia including of the lung, gastrointestinal tract (particularly in the enteric neurons) and pancreas. The expression in these organs occurred in a spatially restricted manner. In the CNS, the expression was highly compartmentalized in the dorsal thalamus, cerebellum and medulla. The expression compartment in the thalamus in which Slitrk6 was expressed was closely related to the Gbx2-expressing prosomere 2. Interestingly, the Slitrk6 expression in the CNS, cochlea, tongue, tooth primordial, and other organs was partially complementary to the expression of Nlrr3, which belongs to another family of neuronal LRR-containing transmembrane proteins. The complementary expression of the two proteins in the dorsal thalamus persisted from E13.5 to the adult stage.     

添加丙氨酰谷氨酰胺的胃肠外营养对存在营养风险的胃癌根治术患者免 疫功能、营养状态及术后恢复的临床意义*

目的:本研究旨在探讨NRS评分大于5分的胃癌根治术患者围手术期应用丙氨酰谷氨酰胺(Ala-Gln)强化的肠外营养对免疫功能、营养状况及术后恢复情况的临价值。方法:NRS-2002评分大于5分的胃癌患者60例,随机分为两组,每组30例。术前开始给予肠外营养支持,5日后手术,手术方式为根治性胃切除,包括远端胃大部切除术和全胃切除术。术后继续给予常规肠外营养。只有实验组给予谷氨酰胺双肽每日20克。于入院时和手术后第6日测量CD4、CD8、CD4/CD8、IgG、IgA、IgM淋巴细胞计数等免疫指标,血清总蛋白、白蛋白、谷丙转氨酶、总胆红素、血肌酐等肝肾功能指标,观察手术恢复过程及术后并发症发生情况。结果:采用谷氨酰胺强化的试验组CD4、CD8等免疫指标恢复情况显著优于对照组。二者一过性肝功能损伤发生率无明显差异。但试验组白蛋白较对照组恢复迅速。试验组术后肠蠕动恢复较对照组快,术后腹泻发生率较低。两组在术后抗生素应用时间、术后感染等发病率方面未显示统计学差异。结论:对存在营养风险的胃癌患者进行围手术期静脉营养支持时添加谷氨酰胺制剂可明显改善患者的免疫状况,促进术后恢复减少手术并发症。     

凋亡相关基因bcl-2和Bax在大鼠应激性溃疡中的表达及作用

目的探讨凋亡相关基因bcl-2和Bax在应激性溃疡中表达的变化及中药组方应激宁对其变化的影响。方法Wistar大鼠水浸-束缚应激(WRS)4h,用免疫组织化学方法检测胃黏膜组织bcl-2和Bax蛋白的表达。结果bcl-2和Bax在正常大鼠胃黏膜组织中有散在的表达;应激宁组bcl-2阳性细胞数目较应激组增多,两者具有明显的差异(P<0.05);应激组Bax阳性细胞数目较应激宁组增多,两者也具有明显的差异(P<0.05);在应激组和应激宁组中,Bax阳性细胞数目均比bcl-2增加(P<0.05)。结论WRS后胃黏膜组织bcl-2和Bax的表达差异很可能参与了胃黏膜损伤和修复过程,应激宁对胃黏膜的损伤具有一定的保护作用。     

灵光注射液对失血性休克大鼠胃肠粘膜的保护作用

目的　观察灵光注射液 (复方樟柳碱 )对失血性休克再灌注大鼠胃肠粘膜损伤的影响。方法　将 5 6只雄性Wistar大鼠随机分 4组 ,分别设为假休克组 (8只 )、模型组 (16只 )、灵光注射液低剂量组 (16只 )和高剂量组(16只 ) ,除假休克组外 ,大鼠均经历 4kPa ,70min的失血性休克 ,在休克复苏后 6h和 12h各组分别处死半数动物 ,观察大鼠肠道菌移位情况、病理组织学和超微结构变化。结果　灵光注射液对大鼠失血性休克再灌注引起的肠道细菌移位和胃肠粘膜形态损伤有明显的保护作用 ,其治疗机制可能与改善微循环、清除氧自由基作用有关     

Stimulatory effects of endogenous and exogenous nitric oxide on gastric acid secretion in anesthetized rats

We previously reported the stimulatory effect of endogenous nitric oxide (NO) on gastric acid secretion in the isolated mouse whole stomach and histamine release from gastric histamine-containing cells. In the present study, we investigated the effects of endogenous and exogenous NO on gastric acid secretion in urethane-anesthetized rats. Acid secretion was studied in gastric-cannulated rats stimulated with several secretagogues under urethane anesthesia. The acid secretory response to the muscarinic receptor agonist bethanechol (2 mg/kg, s.c.), the cholecystokinin(2) receptor agonist pentagastrin (20 microg/kg, s.c.) or the centrally acting secretagogue 2-deoxy-D-glucose (200 mg/kg, i.v.) was dose-dependently inhibited by the NO synthase inhibitor N(omega)-nitro-L-arginine (L-NNA, 10 or 50 mg/kg, i.v.). This inhibitory effect of L-NNA was reversed by a substrate of NO synthase, L-arginine (200 mg/kg, i.v.), but not by D-arginine. The histamine H(2) receptor antagonist famotidine (1 mg/kg, i.v.) completely inhibited the acid secretory response to bethanechol, pentagastrin or 2-deoxy-D-glucose, showing that all of these secretagogues induced gastric acid secretion mainly through histamine release from gastric enterochromaffin-like cells (ECL cells). On the other hand, histamine (10 mg/kg, s.c.)-induced gastric acid secretion was not inhibited by pretreatment with L-NNA. The NO donor sodium nitroprusside (0.3-3 mg/kg, i.v.) also dose-dependently induced an increase in acid secretion. The sodium nitroprusside-induced gastric acid secretion was significantly inhibited by famotidine or by the soluble guanylate cyclase inhibitor methylene blue (50 mg/kg, i.v.). These results suggest that NO is involved in the gastric acid secretion mediated by histamine release from gastric ECL cells.