Effects of Several Denervation Procedures on Distribution of Calcitonin Gene-Related Peptide and Substance P Immunoreactive in Rat Stomach

The effect of chemical deafferentation, vagotomy(VGX), and gangliosympathectomy (GSX) on the density offibers containing calcitonin gene-related peptide (CGRP)and substance P (Sub.P) in the rat gastric wall was studied. Chemical deafferentation bycapsaicin abolished the density of CGRP-immunoreactive(IR) fibers, not Sub.P-IR fibers. Ten days after VGX,the density of CGRP-IR or Sub.P-IR fibers in the mucosa was largely reduced, while no reductionof CGRP-IR and Sub.P-IR fibers was seen in submucosaland muscular layers. GSX significantly reduced thedensity of CGRP-IR fibers in the mucosa and caused a moderate decrease in the fibers in submucosaland muscular layers. Pretreatment with6-hydroxydopamine, a neurotoxin for noradrenergicnerves, did not affect the density of CGRP-IR fibers inthe gastric wall. The density of Sub.P-IR fibers in thegastric wall was not affected by GSX. These studiesindicate that the CGRP-IR and Sub.P-IR fibers in themucosa are susceptible to extrinsic nerve denervation compared with those in the submucosa and musclelayers, that a major portion of the CGRP-IR fibers inthe mucosa is of both vagal and spinal origin, and thata major portion of the Sub.P-IR fibers in the mucosa is of vagal origin. Furthermore, thepresent results support that CGRP-IR fibers, notSub.P-IR fibers, in the rat stomach arecapsaicin-sensitive.     

补中益气汤对“脾虚”大鼠胃粘膜易损伤性的复健作用研究

给大鼠灌胃大黄水提取液１０天，造成类“脾虚”模型进行胃粘膜损伤试验。结果表明该模型对消炎痛、应激因素引起的胃粘膜损伤指数明显高于正常对照组，经补中益气汤治疗７天，其胃粘膜损伤指数较非治疗组明显下降，提示“脾虚”大鼠胃粘膜易损伤性增高，补中益气汤对其有复健作用。     

活体胃血供的特点及其临床意义

目的 了解活体胃血供的特点，旨在探索中晚期胃癌的局部灌注化疗方法。方法 对36例胃溃疡患者在行胃大部切除治疗时，进行亚甲蓝染色，观察活体胃各分支动脉自然血供区域和血流阻断后血供范围的变化。结果 术中见左、右胃网膜动脉和左、右胃动脉分别为胃大、小弯近、远段相应区域提供血液，胃壁组织染色时间很短；阻断动脉血流后，染色范围扩展，染色时间延长；阻断伴行静脉后，染色范围进一步扩展，染色时间再度延长。结论 胃左动脉和胃网膜右动脉为胃血供的主要动脉，其他动脉分支为辅助性动脉；一般情况下，经动脉灌注的亚甲蓝在胃组织停留时间极短；阻断伴行静脉后，可使该染料在组织停留时间延长。推测此法可使化疗药物在胃组织中存留时间延长，从而有利于胃癌的局部化疗。     

Protection Against Chemically-Induced Oxidative Gastrointestinal Tissue Injury in Rats by Bismuth Salts

Oxygen free radicals (OFR) are implicated in thepathogenesis of stress, chemically induced gastriclesions, and gastrointestinal injury. Theconcentration-dependent scavenging abilities of bismuthsubsalicylate (SBS), colloidal bismuth subcitrate (CBS), andselected OFR scavengers, including superoxide dismutase(SOD), catalase, mannitol, and allopurinol were examinedagainst biochemically or chemically generated superoxide anion, hydroxyl radical, andhypochlorite radical plus hypochlorous acid based on achemiluminescence assay. Furthermore, both gastric (GM)and intestinal mucosa (IM) were individually exposed in vitro to these free radical generatingsystems, and the concentration-dependent protectiveabilities of SBS and CBS against lipid peroxidation (LP)were compared with selected OFR scavengers. In addition, 24-hr fasted rats were orally treated with thenecrotizing agents 0.6 M HCl, 0.2 M NaOH, 80% ethanol,and aspirin (200 mg/kg). The extent of tissue injury inthe GM and IM was determined by assessing LP, DNA fragmentation, and membrane microviscosity.Dose- and time-dependent in vivo protective abilities ofCBS (100 mg/kg) and SBS (15 mg/kg) were also assessed.Following incubations with superoxide anion and hydroxyl radical generating systems in thepresence of 125 mg SBS/liter, approximately 47% and 61%inhibitions were observed in the chemiluminescenceresponse, respectively, while 48% and 46% inhibitions were observed with 125 mg CBS/liter. SBS andCBS exerted similar abilities towards hypochloriteradical plus hypochlorous acid. Approx. 3.1- and3.7-fold increases in LP were observed in the GM and IMof rats following oral administration of 0.6 MHCl. Pretreatment of the rats with SBS and CBS decreased0.6 M HCl-induced LP in the GM by approx. 39% and 27%,respectively, with similar decreases in LP in the IM. SBS exhibited better protectiveabilities towards 0.6 M HCl and 0.2 m NaOH-induced GMand IM injury as compared to CBS. SBS and CBS providedsimilar protection towards 80% ethanol-induced gastric injury, while CBS exerted a superior protectiveability towards aspirin-induced gastric injury. Theresults demonstrate that both SBS and CBS can scavengereactive oxygen species and prevent tissue damage produced by OFR.     

中药升降胶囊对大鼠胃排空的影响

[目的]观察中药升降胶囊对大鼠胃排空的影响,并从红细胞乙酰胆碱酯酶活性和血浆胃动素(Mot)、生长抑素(SS)方面探讨其作用机制。[方法]将8周龄的SD大鼠随机分成B组(升降胶囊高剂量组),C组(升降胶囊低剂量组),D组(枳壳白术组),A组(正常对照组)和E组(西沙比利组)。用药10d后用同位素法检测其胃排空功能,微量羟胺法检测其红细胞乙酰胆碱酯酶活性,放免法检测其血浆Mot和SS。[结果]B、C、D组30min胃排空率分别为(51.44±6.38)%、(40.82±7.24)%和(40.22±7.16%,均高于八组的(33.18±6.32)%;3组红细胞乙酰胆碱酯酶活性、MOT和SS分别为:B组(0.856±0.128)μmol/h,(124.26±25.94)ng/L和(39.42±7.%)ng/L,C组(0.726±0.164)μmol/h,(119.86±29.38)ng/L和(38.33±7.64)ng/L,均高于A组的(0.576 ± 0.150)μmol/h,(91.28±26.84)ng/L和(28.22±7.68)ng/L。[结论]升降胶囊可促进胃排空,其机制可能与增强胆碱能神经功能及提高血浆Mot和SS水平有关。     

Delayed Gastric Emptying by Helicobacter pylori Lipopolysaccharide in Conscious Rats

The present study was carried out to investigatethe possibility that lipopolysaccharide deprived fromHelicobacter pylori may alter gastric motility. Toaddress the question, we examined the effect of H. pylori lipopolysaccharide on gastricemptying in conscious rats. Gastric emptying wasevaluated by the phenol red method. Time-course anddose-related effects of intraperitoneal administrationof H. pylori lipopolysaccharide were investigated.Intraperitoneal injection of H. pylorilipopolysaccharide significantly suppressed gastricemptying of a liquid meal in a dose-dependent manner.The inhibitory action of H. pylori lipopolysaccharide wasobserved 2, 4, 8, or 12 hr after the injection. Theseresults suggest for the first time that H. pylorilipopolysaccharide may suppress gastric emptying in along-lasting fashion. It is also suggested that H. pylorimay influence gastric function through its cell wallstructure named lipopolysaccharide.     

Rebamipide Attenuates Indomethacin-Induced Gastric Mucosal Lesion Formation by Inhibiting Activation of Leukocytes in Rats

Granulocyte elastase released from activatedleukocytes plays an important role in leukocyteinfiltration. Since activated leukocytes have been shownto be involved in the pathogenesis of gastric mucosal lesion formation induced by nonsteroidalantiinflammatory drugs, inhibition of granulocyteelastase release from activated leukocytes may be usefulin the prevention of these lesions. Rebamipide, a novel antiulcer agent, inhibited granulocyte elastaserelease from activated neutrophils in vitro. Rebamipideand ONO-5046, a granulocyte elastase inhibitor, markedlyinhibited gastric mucosal lesion formation in rats. Gastric myeloperoxidase activity wassignificantly increased 3 hr after indomethacinadministration. This increase was significantlyinhibited by rebamipide and ONO-5046. Cimetidine did notinhibit granulocyte elastase release from activatedneutrophils. Although cimetidine markedly prevented theindomethacin-induced gastric mucosal lesion formation,it did not reduce the gastric myeloperoxidase activity. Therefore, unlike cimetidine, rebamipide mayprevent indomethacin-induced gastric mucosal lesionformation by inhibiting neutrophil activation.     

Possible Mechanism of Increase in Gastric Mucosal PGE2 and PGI2 Generation Induced by Ecabet Sodium, a Novel Gastroprotective Agent

The gastroprotective agent ecabet sodium(ecabet, 12-sulfodehydroabietic acid monosodium salt)increases the formation of prostaglandin (PG)E₂ and I₂ by gastric mucosa. Inthe present study, we examined the effect of ecabet on metabolism ofarachidonic acid (AA) in rat gastric mucosal cells.Ecabet (0.1-10 mM) concentration- and time-dependentlypotentiated the release of [¹⁴C]AA fromgastric mucosal cells prelabeled with [¹⁴C]AA andsimultaneously increased the production ofPGE₂ and PGI₂. The ecabet-mediatedincreases in [¹⁴C]AA release andPGE₂ production were both partly depressed bymepacrine (30 and 100 M) and Ca²⁺ chelation.Ecabet, however, showed no effect on gastricphospholipase A₂ (PLA₂) activityand [Ca²⁺]_i in the gastric mucosalcells. Ecabet and other dehydroabietic acid derivatives, 12-carboxydehydroabietic acid monosodium saltand mono[16-(12-sulfodehydroabietyl)]succinic acidmonosodium salt, which potentiated the liberation of[¹⁴C]AA, increased the membrane fluidity ofgastric mucosal cells assessed by usingdiphenylhexatrienepropionic acid (DPH-PA) as the probe,while 12-sulfamoyldehydroabietic acid showed no effecton either the AA liberation or the membrane fluidity.Ecabet (0.1-10 mM) increased the membrane fluidityconcentration- and time-dependently in accordance withits facilitating effect on AA release. In conclusion,ecabet increases the synthesis of PGE₂ andPGI₂ by gastric mucosal cells through promoting the release ofAA, which is partly dependent on PLA₂ andCa²⁺. The ecabet-induced increase in membranefluidity may be involved in part 2 in the liberation ofAA from the gastric mucosal cells.     

Role of Nitric Oxide in Oxidative Damage in Isolated Rabbit Gastric Cells Exposed to Hypoxia-Reoxygenation

The present study aimed to investigate the roleof nitric oxide on the oxidative damage in isolatedrabbit gastric cells exposed to hypoxia-reoxygenation.Nitric oxide synthesis modulators such as L-arginine and N^G-nitro-L-arginine methylester, a nitric oxide donor, sodium nitroprusside, andsuperoxide dismutase were used to treat the cells, andthe synthesis and secretion of mucus, lipid peroxideproduction, and glutathione contents of the cells weredetermined. As a result, hypoxia-reoxygenation decreasednitric oxide production and the synthesis and secretionof mucus, as well as glutathione contents of gastric cells, but hypoxia-reoxygenation increasedlipid peroxide production. Pretreatment with L-arginine,a substrate for nitric oxide synthase, sodiumnitroprusside, and superoxide dismutase prevented theincrease in lipid peroxide production and the decreasesin glutathione contents, as well as the synthesis andsecretion of mucus induced by hypoxia-reoxygenation.However, N^G-nitro-L-arginine methyl ester, anitric oxide synthase inhibitor, had no effect onthese alterations. In conclusion, nitric oxide has anantioxidant defensive role on gastric cells bymaintaining mucus and glutathione.     

Gastric Mucosal Injury Induced by Local Ischemia-Reperfusion in Rats (Role of Endogenous Endothelin-1 and Free Radical)

We investigated the role of an endogenousvasoconstrictor peptide endothelin-1 (ET-1) and freeradicals in local gastric ischemia-reperfusion injury inrats. Local gastric ischemia was induced by clamping the left gastric artery for 15 min andreperfusion was done for 10-30 min in the presence of150 mM exogenous HCl intragastrically. Local gastricischemia and reperfusion resulted in significantmacroscopic and microscopic gastric mucosal damage togetherwith elevation of gastric tissue ET-1 concentration.Gastric tissue ET-1 was found to increase after 15 minof ischemia alone and also with 30 min of reperfusion. A novel nonpeptide endothelin receptorantagonist, bosentan, or a combination of radicalscavengers (superoxide dismutase, catalase, anddeferoxamine) both attenuated gastric mucosal injury.However, the greater protection observed with bosentan thanwith radical scavengers might reflect a preferentialrole of endothelin-1 in this type of injury.