链脲佐菌素诱导的糖尿病大鼠的胃酸分泌变化：对各种促分泌剂的不同反应。

Acid secretory changes in streptozotocin-diabetic rats: different responses to various secretagogues.

作者信息

Tashima K, Nishijima M, Fujita A, Kubomi M, Takeuchi K

机构信息

Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Japan.

出版信息

Dig Dis Sci. 2000 Jul;45(7):1352-8. doi: 10.1023/a:1005556003938.

DOI:10.1023/a:1005556003938

PMID:10961714

Abstract

We examined gastric acid secretion in response to various stimuli in streptozotocin (STZ) induced diabetic rats and characterized the alteration of acid secretory responses in diabetic conditions. Animals were injected STZ (70 mg/kg, intraperitoneally) and used after five weeks of diabetes with blood glucose >350 mg/dl. Under urethane anesthesia, the experiment was performed in a chambered stomach or a whole stomach preparation, and the acid secretion was measured at pH 7.0 using a pH-stat method and by adding 100 mM NaOH. The acid secretion was stimulated by intravenous infusion of either histamine (4 mg/kg/hr), pentagastrin (60 microg/kg/hr), or carbachol (20 microg/kg/hr) or by intraluminal application of peptone solution (4%), or vagal electrical stimulation (2 msec, 3 Hz, 0.5 mA). In normal rats, acid secretion was increased in response to either histamine, pentagastrin, carbachol, peptone, or electrical vagal stimulation. In STZ diabetic rats, however, changes in acid secretion varied depending on the stimuli; the acid response to histamine remained unchanged, but the responses to vagal electrical stimulation or pentagastrin and carbachol were significantly decreased or enhanced, respectively, as compared to normal rats. Likewise, the acid response to peptone was also markedly enhanced in STZ-diabetic rats, and this response was significantly blocked by atropine and YM022 (a CCKB/gastrin antagonist) as well as famotidine in both normal and diabetic rats. Both pentagastrin and carbachol increased the luminal release of histamine in normal rats, and these responses were significantly augmented in STZ-diabetic rats. The altered acid response and histamine release induced by pentagastrin in STZ diabetic rats were partially reversed by daily injection of insulin. These results suggest that STZ-diabetic rats showed different changes in gastric acid secretion in response to various stimuli. The increased acid secretory response may be associated with an enhanced release of mucosal histamine, while the decreased response may be due to vagal neuropathy.

摘要

我们研究了链脲佐菌素（STZ）诱导的糖尿病大鼠对各种刺激的胃酸分泌情况，并对糖尿病状态下胃酸分泌反应的改变进行了特征描述。给动物腹腔注射STZ（70 mg/kg），在糖尿病持续五周且血糖>350 mg/dl后使用。在氨基甲酸乙酯麻醉下，实验在有腔胃或全胃标本上进行，使用pH计法并加入100 mM NaOH在pH 7.0时测量胃酸分泌。通过静脉输注组胺（4 mg/kg/hr）、五肽胃泌素（60 μg/kg/hr）或卡巴胆碱（20 μg/kg/hr），或通过腔内注入蛋白胨溶液（4%），或迷走神经电刺激（2毫秒，3赫兹，0.5毫安）来刺激胃酸分泌。在正常大鼠中，对组胺、五肽胃泌素、卡巴胆碱、蛋白胨或迷走神经电刺激的反应会使胃酸分泌增加。然而，在STZ糖尿病大鼠中，胃酸分泌的变化因刺激因素而异；与正常大鼠相比，对组胺的酸反应保持不变，但对迷走神经电刺激或五肽胃泌素和卡巴胆碱的反应分别显著降低或增强。同样，STZ糖尿病大鼠对蛋白胨的酸反应也明显增强，并且在正常和糖尿病大鼠中，这种反应都被阿托品、YM022（一种CCKB/胃泌素拮抗剂）以及法莫替丁显著阻断。五肽胃泌素和卡巴胆碱均可增加正常大鼠腔内组胺的释放，在STZ糖尿病大鼠中这些反应显著增强。在STZ糖尿病大鼠中，五肽胃泌素诱导的酸反应改变和组胺释放可通过每日注射胰岛素部分逆转。这些结果表明，STZ糖尿病大鼠对各种刺激的胃酸分泌表现出不同的变化。胃酸分泌反应增加可能与黏膜组胺释放增强有关，而反应降低可能是由于迷走神经病变。