侧脑室注射雨蛙肽对应激性胃粘膜损伤的影响

本工作研究了向侧脑室注射雨蛙肽对束缚四肢再浸水引起大鼠应激性胃粘膜损伤的影响及机制。侧脑室注射雨蛙肽(1.0ng/rat)可显著减轻胃粘膜损伤,抑制胃酸分泌,促进胃壁结合粘液分泌并使胃液中PGE_2含量增加。电镜观察可见胃壁细胞分泌增强。预先侧脑室注射纳洛酮或皮下注射消炎痛可消除雨蛙肽抗胃粘膜损伤和抑制胃酸分泌的效应,但对胃壁结合粘液分泌无影响。侧脑室注射阿托品、酚妥拉明、心得安不影响雨蛙肽的抗损伤作用。上述结果提示:注射到侧脑室的雨蛙肽的抗胃粘膜损伤作用,部分是通过中枢的吗啡受体和促进内源性PGE_2合成而实现的。     

损毁中缝大核对大鼠胃酸排出量及血清胃泌素水平的影响

本实验观察了损毁中缝大核对大鼠胃酸排出量和血清胃泌素水平的影响。实验表明:损毁中缝大核可增加胃酸排出量和血清胃泌素水平。切断双侧膈下迷走神经干可以消除这种作用,去除腹腔交感神经节及肠系膜上交感神经节只能部分减弱这种作用。     

雌激素和孕激素对切除卵巢大鼠血清胃泌素水平和胃酸分泌的影响

卵巢切除两周后大鼠血清胃泌素水平升高和胃酸分泌增加;给予苯甲酸雌二醇(10μg/d)可完全阻止这两种变化,但补充黄体酮(0.2mg/d)对卵巢切除大鼠的血清胃泌素水平无影响,仅明显减少胃酸分泌。本实验结果提示,雌激素对于雌性大鼠的胃泌素释放和胃酸分泌具有抑制作用,孕激素也有抑制胃酸分泌的作用,这些作用不是摄食量改变的结果.     

血清胃泌素变化与急性胃粘膜病变关系的研究

对大白鼠血清中胃泌素水平的变化与急性胃粘膜病变的关系进行了初步的研究,结果表明以消炎痛为诱因引起的急性胃粘膜病变大白鼠血清胃泌素水平明显增高。而维酶素可以抑制因消炎痛引起的急性胃粘膜病变时血清胃泌素的释放,对胃粘膜具有保护作用。     

下丘脑室旁核注射神经降压素对大鼠胃酸分泌的影响及机制探讨

本实验用乌拉坦麻醉的大鼠,探讨了下丘脑室旁核（ＰＶＮ）注射神经降压素（ＮＴ）对胃酸分泌的影响及其机制。结果表明,ＰＶＮ注射微量ＮＴ后,胃酸排出量呈剂量依赖性减少,此效应可被侧脑室内预先注射酚妥拉明所阻断,但不能被螺哌啶酮阻断、双侧颈迷走神经切断后,ＰＶＮ注射ＮＴ对胃酸排出量无明显影响。这提示,ＰＶＮ注射ＮＴ对大鼠胃酸分泌的抑制作用,可能与该处α－受体的激活有关,并通过迷走神经所中介。     

兔下丘脑弓状核区在躯体传入冲动抑制刺激下丘脑诱发的期前收缩中的作用

实验在62只乌拉坦、氯醛醣麻醉兔上进行,用三碘季铵酚制动,由人工呼吸机维持通气。电解损毁下丘脑弓状核区或者在该区微量注射纳洛酮(2μg/1μl)可消除刺激腓深神经对刺激下丘脑诱发的期前收缩的抑制作用。在下丘脑弓状核区微量注射吗啡(2μg/1μl)可减少刺激下丘脑诱发的期前收缩次数,而注射纳洛酮(2μg/1μl)则使期前收缩数增多。无论损毁延髓中线区或在中央灰质内微量注射纳洛酮(2μg/1μl),均可消除下丘脑弓状核区微量注射吗啡(2μg/1μl)对刺激下丘脑诱发的期前收缩的抑制作用。因而,在下丘脑弓状核区微量注射吗啡,可能经中脑中央灰质而发挥对刺激下丘脑诱发的期前收缩的抑制作用。     

中脑导水管周围灰质在侧脑室注入微量吗啡或纳洛酮所引起的镇痛或拮抗镇痛中的作用

本工作进一步探索中脑导水管周围灰质(PAG)在吗啡镇痛与纳洛酮拮抗吗啡镇痛中的作用。实验在清醒受限制的大鼠上进行,以电刺激鼠尾出现的甩尾和嘶叫为痛反应指标。结果表明:(1)侧脑室注射微量纳洛酮后,可使电刺激 PAG 或注射微量吗啡于 PAG 所引起的镇痛效应受到明显拮抗;(2)损毀 PAG 或注射微量纳洛酮于 PAG 后,可使由侧脑室注入微量吗啡所引起的镇痛效应显著减弱。由此可见 PAG 既是侧脑室注射吗啡镇痛作用的重要中枢部位,又是侧脑室注射纳洛酮拮抗吗啡镇痛的重要中枢部位。     

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。     

下丘脑室旁核orexin-A对大鼠摄食和胃动力影响及调控机制

目的:探讨下丘脑室旁核orexin-A对大鼠摄食和胃动力影响及调控机制。方法:采用免疫组化观察下丘脑室旁核(paraventricular nucleus,PVN)orexin受体表达情况;PVN注射orexin-A观察大鼠摄食、胃运动、胃酸分泌和胃排空的改变。结果:免疫组化实验显示大鼠PVN中存在orexin受体免疫阳性细胞。PVN注射orexin-A后,大鼠前三小时摄食增加,6 h和24 h摄食无显著改变。PVN微量注射orexin-A后,大鼠胃运动幅度和频率增加、胃排空增快并且胃酸分泌增多。[D-Lys-3]-GHRP-6可部分阻断orexin-A对摄食、胃运动、胃排空和胃酸分泌的促进作用,SB334867可完全阻断orexin-A对胃运动、胃排空和胃酸分泌的促进作用。结论:下丘脑室旁核orexin-A可能通过生长激素促泌素GHSR受体信号通路调控大鼠摄食及胃功能。     

下丘脑外侧区注入胃泌素对大鼠胃酸分泌的影响

本工作观察了下丘脑外侧区(LHA)、腹内侧核(VMH)或侧脑室(LCV)注射17肽胃泌素(G17)或五肽胃泌素(G5)对清醒大鼠胃酸分泌的影响。结果表明,将 G17或 G5注入 LHA可引起胃酸分泌明显增加,而将 G5注入 VMH、LCV 或静脉则不影响胃酸分泌;切断迷走神经可以阻断在 LHA 注入 G5引起胃酸分泌增加的效应;在阿托品背景下,将 G5注入 LHA仍能引起胃酸分泌明显增加;静脉注射酚妥拉明,心得安或纳洛酮均不影响 G5对 LHA 刺激胃酸分泌的作用。这些结果提示:LHA 是胃泌素作用的一个特异性部位,由 LHA 发出的冲动可能通过迷走神经内的两种传出纤维引起胃酸分泌,一为胆碱能纤维,另一为非胆碱能非肾上腺素能纤维。     

Effects of morphine, enkephalins and naloxone on postprandial gastric acid secretion, gastric emptying and gastrin release in dogs

The effects of intravenous infusions of morphine, met-enkephalin and leu-enkephalin on gastric acid secretion, gastrin release and gastric emptying were investigated in four dogs with gastric cannulas stimulated by a liquid peptone meal. The actions of a potent opiate antagonist, naloxone, used alone or combined with opiates were also studied. Morphine, met-and leu-enkephalin decreased the fractional gastric emptying rate. Acid secretion was decreased by enkephalins and increased by high doses of morphine. Enkephalins and to a lesser degree morphine inhibited gastrin release during the first hour following the administration of the meal. Only leu-enkephalin decreases significantly the integrated gastrin response. Naloxone at the doses used antagonized partly or totally the effects of opiates on gastric emptying but not those on gastric secretion or gastrin release. Naloxone infused alone had no significant effect on the gastric functions tested. These studies indicate that in dogs stimulated by a liquid test meal, enkephalins inhibit gastric emptying, acid secretion and gastrin release. Morphine inhibits gastric emptying and gastrin release and enhances acid secretion.     

Centrally administered NPY stimulated gastric acid and pepsin secretion by a vagally mediated mechanism

We investigated the possible roles of centrally administered neuropeptide Y (NPY) on gastric secretion, serum gastrin levels and gastric mucosal blood flow in anesthetized rats. Centrally administered NPY dose-dependently stimulated gastric acid and pepsin secretion. The stimulatory effect of intracerebroventricular administration of NPY was more potent than that of intracisternal administration. Centrally administered NPY also increased gastric secretion in the central noradrenaline depleted rats. In contrast, intravenously administered NPY had no influence on gastric secretion. These stimulatory effects were abolished by vagotomy or atropine pretreatment. The serum gastrin levels did not change after central NPY injection. Although intravenously administered NPY slightly increased gastric mucosal blood flow, centrally administered NPY slightly diminished gastric mucosal blood flow. These results indicate that centrally administered NPY markedly influences gastric functions in the rat.     

Effect of met-enkephalin and morphine on gastric secretion and blood flow

The effects of met-enkephalin and morphine on gastric acid and pepsin secretion and gastric mucosal and total blood flow were studied in anaesthetized dogs with an in vivo chambered secretion stomach preparation. It was found that both agents infused intraarterially caused an increase in histamine-induced acid and pepsin secretion and mucosal and total blood flow. The above responses were significantly blocked by naloxone and nalorphine. In the resting stomach both opiates did not induce secretory changes but they increased mucosal and total blood flow. Met-enkephalin and morphine were also effective after intravenous administration. Met-enkephalin but not morphine fails to stimulate acid secretion if given into the portal vein. The likely mechanism of action of opiates on gastric secretion is discussed and a hypothesis of existence of opiate receptors in the gastric wall is presented.     

A study of the actions of naloxone and morphine on gastric acid secretion and gastric mucosal damage in the rat

There exists a considerable controversy in the literature with regard to the effect of either opiate receptor blockade or that of morphine in different gastric and intestinal ulcer models in the rat. We performed experiments to evaluate the effects of naloxone and morphine on gastric acid secretion and gastric mucosal damage in different experimental models of gastric mucosal injury, namely in indomethacin-, HCl (0.6N)- and ethanol (96%)-models. We found that: 1) 10 mg/kg naloxone ip given twice, effectively protected gastric mucosa against indomethacin (30 mg/kg ip) and against the acid-dependent injury caused by 0.6 N HCl (1 mL ig), but not against the non acid-dependent injury caused by 96% ethanol (1 mL ig); 2) morphine (10 + 10 mg/kg ip) increased ulcers in the HCl-model, but had no effect in the two other models; 3) this ulcer-aggravating effect of morphine in the HCl-model was blocked by pretreatment of 2 mg/kg ip naloxone; and 4) both naloxone (5 + 5 and 10 + 10 mg/kg ip) significantly decreased gastric acid secretion in 1-h pylorus ligated rats. We conclude that: 1) naloxone dose-dependently protects against the indomethacin- and HCl-, but not against the ethanol-induced gastric mucosal damage; 2) morphine aggravates the HCl-induced ulcerogenesis; and 3) both opiod receptor agonist and antagonist decrease gastric acid secretion.     

Suppression of gastric acid secretion by intracisternal bombesin does not require the ventromedial hypothalamus

Intracisternal administration of the tetradecapeptide peptide bombesin suppresses gastric acid release. Other studies have shown that the ventromedial hypothalamus (VMH) may have an inhibitory role in gastric regulation. To determine if the inhibition of gastric acid secretion by intracisternally administered bombesin is mediated by the ventromedial hypothalamus, bombesin was injected intracisternally in rats with ventromedial hypothalamic lesions. Neither anterior nor posterior VMH lesions altered the effects of bombesin on gastric acid, concentration, volume, total output, or on serum gastrin. The bombesin-induced rise in gastric pH was very mildly attenuated by both lesions. The previous finding of enhanced gastric acid secretion after anterior VMH lesions was confirmed. The results suggest that the VMH is not crucial in the bombesin-induced inhibition of acid secretion.     

Inhibition of gastric acid secretion by intracerebral injection of calcitonin gene related peptide in rats

Calcitonin gene related peptide (CGRP), a 37 amino acid peptide recently characterized from the rat brain, injected into the cisterna magna or the lateral hypothalamus, inhibited gastric acid secretion and increased serum gastrin levels in conscious pylorus-ligated rats. CGRP suppressed pentagastrin- and histamine-induced stimulation of gastric secretion in urethane-anesthetized gastric fistula rats. Peptide action was dose-dependent, not modified by adrenalectomy and peripheral sympathectomy induced by guanethidine pretreatment and reversed by vagotomy. These results demonstrate that intracisternal or intralateral hypothalamic injection of CGRP inhibits stimulated gastric acid secretion. The mechanism of action is vagal dependent and unrelated to modification of gastrin secretion or activation of sympathetic outflow.     

Relation of endogenous opioid peptides and morphine to neuroendocrine functions.

Morphine and the endogenous opioid peptides (EOP) exert similar effects on the neuroendocrine system. When adminstered acutely, they stimulate growth hormone (GH), prolactin (PRL), and adrenocorticotropin (ACTH) release, and inhibit release of luteinizing hormone (LH), follicle stimulating hormone (FSH),and thyrotropin (TSH). Recent studies indicate that the EOP probably have a physiological role in regulating pituitary hormone secretion. Thus injection of naloxone (opiate antagonist) alone in rats resulted in a rapid fall in serum concentrations of GH and PRL, and a rise in serum LH and FSH, suggesting that the EOP help maintain basal secretion of these hormones. Prior administration of naloxone or naltrexon inhibited stress-induced PRL release, and elevated serum LH in castrated male rats to greater than normal castrate levels. Studies on the mechanisms of action of the EOP and morphine on hormone secretion indicate that they have no direct effect on the pituitary, but act via the hypothalamus. There is no evidence that the EOP or morphine alter the action of the hypothalamic hypophysiotropic hormones on pituitary hormone secretion; they probably act via hypothalamic neurotransmitters to influence release of the hypothalamic hormones into the pituitary portal vessels. Preliminary observations indicate that they may increase serotonin and decrease dopamine metabolism in the hypothalamus, which could account for practically all of their effects on pituitary hormone secretion.     

Separate hypoglycaemic thresholds for gastric acid and pepsin secretion following insulin or posterior hypothalamic stimulation.

The level of hypoglycaemia required to elicit gastric secretion of acid and pepsin was studied in urethane-anaesthetized rats. Hypoglycaemia was induced by intravenous injection of insulin or by electrical stimulation of the posterior hypothalamus. In each case the blood glucose values below which gastric secretion was stimulated were significantly higher for pepsin than for acid secretion. This consistently resulted in the onset of pepsin secretion in advance of the onset of acid secretion. These observations suggest that the production of the different components of the gastric juice was under the influence of either separate hypothalamic glucoreceptors, or a single set of glucoreceptors able to respond selectively to different blood glucose levels.