大鼠浸水应激性胃粘膜损伤机制的研究

本工作观察了室温下单纯束缚加生理盐水,浸水应激加生理盐水,浸水应激加阿托品(0.5mg/kg),浸水应激加酚苄明(10mg/kg),浸水应激加戊巴比妥钠(30mg/kg)5组大鼠的胃粘膜损伤程度,胃酸分泌,胃壁结合粘液分泌和胃运动的变化。结果表明:大鼠浸水应激后胃粘膜损伤严重,胃酸分泌增加,胃壁结合粘液分泌减少,胃运动亢进;预先应用阿托品再浸水应激可显著减轻胃粘膜损伤程度,抑制胃酸分泌和胃运动,但增加胃壁结合粘液的分泌;预先应用应巴比妥钠亦显著减轻胃粘膜损伤程度,抑制胃运动和增加胃壁结合粘液的分泌,但对胃酸分泌无影响;预先应用酚苄明对胃粘膜损伤程度、胃酸分泌、胃壁结合粘液分泌和胃运动均无明显影响。上述结果提示,胃运动亢进、胃壁结合粘液分泌减少及胃酸分泌增加均不同程度地参与了浸水应激性胃粘膜损伤的形成,但在胃运动受到抑制及胃壁结合粘液分泌增加的情况下,仅胃酸的存在不致引起胃粘膜严重损伤。     

幽门部在调节胃液分泌中的作用

一般解剖学书上把胃脏远端20%的范围定名为幽门部或胃窦。幽门部粘膜的特点是不含泌酶细胞,此种细胞恰在与胃体部粘膜的交界处即突然消失;它主要由粘液细胞构成。1902年Bayliss 和Starling 从十二指肠粘膜提取出消化道第一个激素——促胰液素(secretin)。这是激素概念在历史上第一次被提出。1906年Edkins受了这个新颖的激素概念的启发,曾注意到幽门部粘膜的组织结构不同于胃体部的粘膜,并用幽门部粘膜提取液给动物静脉注射后,能引起胃液分泌增加。他最后提出理论:食物本身或其化学成分,可刺激幽门部粘膜释放一种活性物质——促胃液素或胃泌素(gastrin);后者通过血液循环作用到胃腺促进其分泌。     

组织胺参与饮水调节

纽约Colgate大学F.S Kraly等最近报告,组织胺和胰岛素均可刺激饮水,这一作用可被组织胺受体(H_1或H_2)阻断剂所阻断。给大鼠皮下注射组织胺可明显地刺激饮水,并在1.25～20mg/kg剂量范围内呈剂量反应关系,产生最大饮水反应的组织胺剂量是20mg/kg。在注射组织胺前10分钟给大鼠腹腔注射组织胺H_1受体阻断剂dexbrompheniramine(DXB),可显著抑制20mg/kg组织胺刺激的饮水(P<0.001)。在DXB2～16mg/kg范围内,随剂量加大,抑制作用加强。16mg/kg的DXB可使组织胺引起的饮水抑制80%。组织胺H_2受体阻断剂甲氰咪胍(C)亦有显著的抑制作用(P<0.05),其有效剂量为32～100mg/     

吗啡和脑啡肽对大鼠基础胃酸分泌的影响

用大鼠作急性实验,腹腔注射乌拉坦麻醉。以恒定速度将37℃的生理盐水自食道插管灌流入胃,收集从幽门插管流出的灌流液,用0.01当量的 NaOH 滴定其酸度,并计算单位时间内的总酸排出量。结果表明:静脉注射吗啡(3mg/kg)后,胃酸分泌增加,在注射后的30分钟时总酸排出量达最高水平,90分钟恢复至基础水平。静脉注射亮啡肽(2mg/kg),胃酸分泌也增加,总酸排出量于注射后20分钟达最高水平,60分钟恢复至基础水平。纳洛酮在一定剂量范围内(1.2—2.6mg/kg)可完全阻断吗啡增加胃酸分泌的作用,如剂量过大,则反增强吗啡对胃酸分泌的作用。     

抑胃多肽并不能抑制胃液分泌

十多年前Brown和Pedersen从猪小肠粘膜提取出一种由43个氨基酸组成的多肽,观察到这种多肽能抑制狗海氏小胃的胃酸分泌,并设想抑制胃酸分泌可能是此种多肽的主要生理作用,因此将它命名为“抑胃多肽”(gastric inhibitory polypeptide,GIP)。但在人体内生理剂量的GIP是否有抑制胃酸分泌作用尚未有定论。最近美国Maxwell等在8个男性受试者静脉滴注五肽胃泌素引起胃液分泌,其剂量从25至74、222、667和2000ng/公斤/小时逐级增加,每种剂量维持30分钟。在另外的实验日还加用GIP 2μg/公斤/小时静脉滴注。结果表明,GIP只抑制剂量为222ng/公斤/小时的五肽胃泌素引起的胃酸分泌,而对其它剂量     

消炎痛对蛋白胨灌流狗胃窦小胃的效应的影响

本工作的目的在于确定内源性前列腺素是否参与在胃泌素释放与作用的机制。用具有胃肠四通瘘的狗进行慢性实验,用蛋白胨溶液灌流隔离的有神经支配的胃窦小胃以引起胃泌素的释放。收集全部泌酸腺区的胃液分泌,测量其酸排出,作为衡量胃窦粘膜释放胃泌素的指标。用消炎痛作为抑制前列腺素合成的药理学工具。 结果指出,消炎痛明显地减低蛋白胨引起的胃酸排出,且随剂量的增加而减低的程度也增大。此外,消炎痛对四肽胃泌素引起的胃酸分泌并无影响。总结以上结果,我们认为,内源性前列腺素似乎参与胃泌素释放的生理机制,但它对胃泌素引起酸分泌的作用并无影响。     

Nesfatin-1及MCH对大鼠胃酸分泌和胃运动的影响

目的:本实验主要探究nesfatin-1对胃运动和胃酸分泌的影响,以及弓状核(ARC)-下丘脑外侧区(LHA)nesfatin-1神经通路在该过程中的作用。方法:采用逆行追踪和免疫组织化学染色实验观察ARC-LHA nesfatin-1神经通路的构成;在体胃运动实验观察nesfatin-1对胃运动的影响以电刺激ARC对胃运动的影响;采用幽门结扎法测量胃液和胃酸分泌量。结果:LHA微量注射nesfatin-1抑制胃运动和胃酸分泌,但是预先注射黑色素浓集激素(MCH)受体拮抗剂PMC-3881-PI减弱nesfatin-1对胃运动和胃酸分泌的抑制作用。电刺激ARC后,胃收缩幅度和频率显著增强,胃酸分泌明显增多。nesfatin-1抗体或PMC-3881-PI对电刺激ARC诱导的胃运动没有显著影响,但是能够改变电刺激ARC诱导的胃酸分泌。结论:ARC-LHA间nesfafin-1通路可调控大鼠胃运动和胃酸分泌,并且黑色素浓集激素也参与调节该过程。     

电针及刺激延脑中缝大核对猫胃电的影响

以记录猫胃体部和胃窦部胃电为指标,对比观察电针或刺激腓总神经与刺激延脑中缝大核对胃电的影响。实验结果表明:在空腹轻度麻醉的状态下,猫胃体部胃电的振幅约为160μV、频率约为4.3次/分;胃窦部胃电的振幅约为370μV、频率约为4.5次/分。电针或刺激腓总神经与刺激中缝大核对猫胃电的影响均以抑制效应为主。在损毁中缝大核之后,电针对胃电的抑制效应大为减弱,提示中枢的下行性抑制参与了电针对胃电的抑制作用。切割脊髓背外侧索或分别切断双侧的迷走神经,内脏大、小神经,均能减弱下行性抑制对胃电的影响。刺激中缝核的邻近结构,能兴奋猫的胃电,推测在延脑水平还可能存在“下行性兴奋系统”。     

消炎痛对五肽胃泌素引起的大鼠胃酸分泌的影响

本工作进一步证实了消炎痛对胃泌素刺激胃酸分泌作用并无影响。基本应用 Ghosh 和Schild 的方法,用大鼠进行了急性实验,以恒速将接近体温的生理盐水自食道插管灌流胃,从幽门插管收集流出的灌流液作为胃液样品。结果表明,口服消炎痛(20—50mg/kg)对静脉注射五肽胃泌素(10μg/kg)所引起的胃酸分泌并无任何影响,这一结果与我们在狗身上的观察一致。结合前一工作,我们认为,内源性 PG 不影响胃泌素刺激胃酸分泌的作用,但影响胃泌素的合成和释放,因而内源性 PG 可能参与胃液分泌的调节。     

針刺狗“足三里”对組織胺引起的胃液分泌的影响

本工作系以6只不同慢性胃手术狗(巴氏小胃、胃瘘、海氏小胃)为实验对象,連续注射组织胺于皮下,在引起恆定胃液分泌的背景下,观察针刺“足三里”或非穴位点,疼痛刺激,戊巴比妥纳麻醉后针刺“足三里”等情况对胃液分泌的影响,结果表明: (1) 针刺“足三里”可使各种不同慢性胃手术狗的组织胺胃液分泌量和胃蛋白酶增多,胃酸(游离酸和总酸)则无明显变化。针刺非穴位对胃液分泌量、酶和酸度均无显著影响。 (2) 强烈针刺狗前腿皮肤使产生防御反射,使组织胺胃液分泌受到显著抑制,可见足三里对胃液分泌的促进作用具有一定的特异性。 (3) 用戊巴比妥纳麻醉动物后,则上述针刺“足三里”的效应消失,而且此时由组织胺所引起的持续性胃液分泌水平较不麻醉时低。故推测针刺“足三里”的效应可能与神经系统有关。     

Influence of the position of the side chain hydroxy group on the gastric antisecretory and antiulcer actions of E1 prostaglandin analogs

The influence of transposing the C-15 hydroxy group of prostaglandin E₁ methyl ester (PGE₁ME) on gastric antisecretory and antiulcer actions was investigated. The compound (±)15-deoxy- 16,β-hydroxy PGE₁ME (SC-28904) was equipotent to the reference standard PGE₁ME in suppressing histamine-stimulated gastric secretion in the Heidenhain pouch (HP) dog. In contrast to PGE₁ME, SC-28904 was longer acting when administered intravenously and also showed significant oral activity in the histamine-stimulated gastric fistula dog. SC-28904 was also equipotent to PGE₁ME (range of active doses of 0.5 to 5.0 mg/kg, s.c.) in inhibiting forced-exertion gastric ulceration in rats.

The compound (±)15-deoxy- 17,β-hydroxy PGE₁ME (SC-30693) was an inactive antisecretory agent in the dog at the 1.0 mg/kg i.v. bolus dose. This dose was 100 times greater than the active antisecretory dose of PGE₁ME. Likewise, SC-30693, when administered subcutaneously at a 5.0 mg/kg dose, was also totally inactive in preventing gastric ulcers induced by forced exertion in rats.

The important implications of this work are that some of the receptor sites for the PGE₁ molecule could easily accommodate the side chain hydroxy group either in the C-15 or C-16 position. Moreover, the hydroxy group in the latter position significantly improved the biological activity of PGE₁ME.     

Discovery, synthesis, and biological evaluation of novel pyrrole derivatives as highly selective potassium-competitive acid blockers

To discover a gastric antisecretory agent more potent than existing proton pump inhibitors, novel pyrrole derivatives were synthesized, and their H(+),K(+)-ATPase inhibitory activities and inhibitory action on histamine-stimulated gastric acid secretion in rats were evaluated. Among the compounds synthesized, compound 17a exhibited selective and potent H(+),K(+)-ATPase inhibitory activity through reversible and K(+)-competitive ionic binding; furthermore, compound 17c exhibited potent inhibitory action on histamine-stimulated gastric acid secretion in rats and Heidenhain pouch dogs.     

Influence of the position of the side chain hydroxy group on the gastric antisecretory and antiulcer actions of E1 prostaglandin analogs.

The influence of transposing the C-15 hydroxy group of prostaglandin E1 methyl ester (PGE2ME) on gastric antisecretory and antiulcer actions was investigated. The compound (+/-)15-deoxy- 16alpha, beta-hydroxy PGE1ME (SC-28904) was equipotent to the reference standard PGE1ME in suppressing histamine-stimulated gastric secretion in the Heidenhain pouch (HP) dog. In contrast to PGE1ME, SC-28904 was longer acting when administered intravenously and also showed significant oral activity in the histamine-stimulated gastric fistula dog. SC-28904 was also equipotent to PGE1ME (range of active doses of 0.5 to 5.0 mg/kg, s.c.) in inhibiting forced-exertion gastric ulceration in rats. The compound (+/-)15-deocy-17alpha, beta-hydroxy PGE1ME (SC-30963) was an inactive antisecretory agent in the dog at the 1.0 mg/kg i.v. bolus dose. This dose was 100 times greater than the active antisecretory dose of PGE1ME. Likewise, SC-30693, when administered subcutaneously at a 5.0 mg/kg dose, was also totally inactive in preventing gastric ulcers induced by forced exertion in rats. The important implications of this work are that some of the receptor sites for the PGE1 molecule could easily accomodate the side chain hydroxy group either in the C-15 or C-16 position. Moreover, the hydroxy group in the latter position significantly improved the biological activity of PGE1ME.     

Influence of the position of the side chain hydroxy group on the gastric antisecretory and antiulcer actions of E1 prostaglandin analogs

The influence of transposing the C-15 hydroxy group of prostaglandin E₁ methyl ester (PGE₁ME) on gastric antisecretory and antiulcer actions was investigated. The compound (±)15-deoxy- 16α,β-hydroxy PGE₁ME (SC-28904) was equipotent to the reference standard PGE₁ME in suppressing histamine-stimulated gastric secretion in the Heidenhain pouch (HP) dog. In contrast to PGE₁ME, SC-28904 was longer acting when administered intravenously and also showed significant oral activity in the histamine-stimulated gastric fistula dog. SC-28904 was also equipotent to PGE₁ME (range of active doses of 0.5 to 5.0 mg/kg, s.c.) in inhibiting forced-exertion gastric ulceration in rats.The compound (±)15-deoxy-17α,β-hydroxy PGE₁ME (SC-30693) was an inactive antisecretory agent in the dog at the 1.0 mg/kg i.v. bolus dose. This dose was 100 times greater than the active antisecretory dose of PGE₁ME. Likewise, SC-30693, when administered subcutaneously at a 5.0 mg/kg dose, was also totally inactive in preventing gastric ulcers induced by forced exertion in rats.The important implications of this work are that some of the receptor sites for the PGE₁ molecule could easily accommodate the side chain hydroxy group either in the C-15 or C-16 position. Moreover, the hydroxy group in the latter position significantly improved the biological activity of PGE₁ME.     

Does motilin control interdigestive pepsin secretion in the dog?

Pepsin output in the Heidenhain pouch, plasma motilin concentration, and contractile activity in the pouch and the main stomach were investigated in five dogs. During the interdigestive state, the pepsin output was significantly increased with a cyclic increase in contractile activity in both the pouch and main stomach at approximately 100-min intervals. The plasma immunoreactive motilin (IRM) concentration fluctuated during the interdigestive state, and, peaks of IRM concentration coincided with the maximum pepsin secretory activity. Exogenous administration of motilin (0.5 micrograms/kg-hr) increased contractile activity in the main stomach and pouch quite similar to the natural interdigestive migrating contractions (IMC), and increased pepsin output significantly. Atropine pre-treatment suppressed the naturally-occurring and motilin-induced pepsin output and contractions in the pouch. It is concluded that pepsin output and contractions in the Heidenhain pouch increase in close association with the IMC in the main stomach during the interdigestive state and these cyclic motor and secretory events in the vagally denervated fundic pouch are most likely regulated by motilin through the intramural cholinergic pathway.     

Effect of cortisone acetate on acid secretion induced by histamine, pentagastrin, gastrin and food in dogs]

The effects of long term treatment with cortisone on the gastric secretion induced by histamine, pentagastrin, porcine gastrin and a meal have been investigated in four dogs with both gastric fistula and Heidenhain pouch. Cortisone increased the postcibal acid output and the observed maximal acid response from the pouch to all three exogenous stimuli. The ED 50'S remained unchanged. The same effects although less marked were observed in the innervated stomach. These data indicate that the increased acid secretion observed after long term treatment with cortisone is largely due to an increased secretory capacity of the gastric mucosa. This latter could result from an increase in the number of secretory units or to partial removal of a non competitive inhibitor of gastric secretion.     

荧光定量PCR检测家蚕核型多角体病毒在其宿主体内的增殖动态

为了研究家蚕核型多角体病毒(Bombyx mori nuclear polyhedrosis virus,BmNPV)在其宿主幼虫体内不同组织中的增殖动态,对敏感性家蚕品种306幼虫进行经口定量滴注病毒。在接种后9个时间点,对中肠、血淋巴和脂肪体进行取样。以BmNPV DNA 聚合酶基因(dnapol)指示病毒拷贝数,同时以家蚕细胞质肌动蛋白A3(actin A3)基因作为参比基因,用荧光定量PCR的方法分别检测各个时间点的中肠、血淋巴和脂肪体中病毒的拷贝数。结果表明经口感染2 h,病毒进入中肠;12 h,病毒已经到达血淋巴和脂肪体;再经过约12 h的潜伏期,病毒在各组织中开始快速增殖,到84 h各组织中病毒增殖达到平台期。     

Gastric antisecretory actions of (15S)-15-methyl prostaglandin E2 methyl ester and natural prostaglandin E2 in rhesus monkeys

The gastric antisecretory actions of (15S)-15-methyl prostaglandin E₂ methyl ester (Me-PGE₂) and Prostaglandin E₂ (PGE₂) were evaluated in the unanesthetized gastric fistula rhesus monkey. Secretion was submaximally stimulated by multiple subcutaneous injections of histamine acid phosphate given every hour for four consecutive hours. When a steady-state plateau of gastric secretion was reached, the PG's were administered as a single bolus dose either intravenously (i.v.) or intragastrically (i.g.). Both PG's inhibited histamine-stimulated gastric secretion. The PG's showed greater sensitivity in inhibiting acid concentration while not affecting volume output. Active i.v. and i.g. antisecretory doses of Me-PGE₂ ranged from 3 to 10 μg/kg, while PGE₂ showed significant antisecretory activity at i.v. bolus doses of 30–100 μg/kg and i.g. bolus dose of 1.0 mg/kg. Thus, Me-PGE₂ is estimated to be at least 10 and 300 times more potent than PGE₂ by the i.v. and i.g. administration routes, respectively. These findings indicate that the rhesus monkey shows some similarities to man in responsiveness to gastric secretory inhibition by E-prostaglandins.     

Randomised double blind trial of single dose doxycycline for treating cholera in adults.

OBJECTIVE--To compare the efficacy of a single dose of doxycycline (200 or 300 mg) with the standard multiple doses of tetracycline in patients with cholera. DESIGN--Randomised double blind controlled trial. Patients were given a single 200 mg dose of doxycycline, a single 300 mg dose of doxycycline, or multiple doses of tetracycline (500 mg, six hourly intervals). SETTING--Hospital in Bangladesh treating diarrhoea. PATIENTS--261 Patients aged over 15 admitted to the hospital with severe dehydration due to acute watery diarrhoea associated with Vibrio cholerae. All vibrios isolated from the stools and rectal swabs of patients, including those patients with prolonged excretion of vibrios, were sensitive to tetracycline. The stools of all patients at admission were negative for shigella and salmonella. INTERVENTIONS--All patients received rapid intravenous acetate solution for the first four hours after admission to hospital. They were then entered in the study and randomised. Oral rehydration was started immediately after the intravenous treatment. If signs of severe dehydration reappeared during oral treatment patients were given rapid intravenous acetate solution until dehydration was fully corrected. MAIN OUTCOME MEASURES--Stool output in first 24 hours and till diarrhoea stopped, total intake of oral rehydration fluid, duration of diarrhoea, and excretion of vibrio after receiving antibiotic treatment. RESULTS--The median stool outputs during the first 24 hours (275 ml/kg body weight) and till diarrhoea stopped (296 ml/kg body weight) were significantly higher in patients receiving 200 mg doxycycline as a single dose than in patients receiving either standard tetracycline (242 ml/kg body weight and 254 ml/kg body weight) or 300 mg doxycycline (226 ml/kg body weight and 255 ml/kg body weight). Similarly, median consumption of oral rehydration solution (18.45 l) was significantly higher in patients receiving 200 mg doxycycline than in patients receiving either 300 mg doxycycline (16.10 l) or standard tetracycline (14.80 l). Almost equal numbers of patients in each group required unscheduled intravenous acetate solution to correct dehydration during antibiotic treatment. Patients treated with doxycycline (low or high dose), however, had more prolonged excretion of bacteria. CONCLUSIONS--A single 300 mg dose of doxycycline is as effective as the standard multiple dose tetracycline treatment for cholera in terms of stool output, duration of diarrhoea, vomiting, and requirement for oral rehydration solution.     

The effects of 11-methyl 16,16 dimethyl prostaglandin E2 on gastric acid secretion in man

11-Methyl 16,16 Dimethyl Prostaglandin E₂ (TM-PGE) was administered orally to man in dosages of 2.5, 5, 7.5 and 10 μg/kg. Maximal inhibition of basal secretion was 52 and 78% and submaximal histamine-stimulated secretion 45 and 70% for volume and acid output, respectively. Secretory inhibition was observed for approximately two hours after ingestion of the drug. No effect was observed on serum gastrin levels. Side effects occurred with equal frequency in the placebo and drug groups. TM-PGE is well tolerated and inhibits both basal and submaximal histamine-stimulated acid secretion in man. Further evaluation may prove it to be helpful in the clinical treatment of acid hypersecretory states and peptic ulcer disease.