We examined the gastric mucosal blood flow (GMBF) and ulcerogenic responses following barrier disruption induced by sodium taurocholate (TC) in diabetic rats and investigated the role of capsaicin-sensitive sensory neurons in these responses. 2. Animals were injected streptozotocin (STZ: 70 mg kg(-1), i.p.) and used after 5, 10 and 15 weeks of diabetes with blood glucose levels of > 350 mg dl(-1). The stomach was mounted on an ex-vivo chamber under urethane anaesthesia and exposed to 20 mM TC plus 50 mM HCl for 30 min in the presence of omeprazole. Gastric transmucosal potential difference (PD), GMBF, and luminal acid loss (H+ back-diffusion) were measured before and after exposure to 20 mM TC, and the mucosa was examined for lesions 90 min after TC treatment. 3. Mucosal application of TC caused PD reduction in all groups; the degree of PD reduction was similar between normal and diabetic rats, although basal PD values were lower in diabetic rats. In normal rats, TC treatment caused luminal acid loss, followed by an increase of GMBF, resulting in minimal damage in the mucosa. 4. The increased GMBF responses associated with H+ back-diffusion were mitigated in STZ-treated rats, depending on the duration of diabetes, and severe haemorrhagic lesions occurred in the stomach after 10 weeks of diabetes. 5. Intragastric application of capsaicin increased GMBF in normal rats, but such responses were mitigated in STZ diabetic rats. The amount of CGRP released in the isolated stomach in response to capsaicin was significantly lower in diabetic rats when compared to controls. 6. The deleterious influences on GMBF and mucosal ulcerogenic responses in STZ-diabetic rats were partially but significantly antagonized by daily insulin (4 units rat(-1)) treatment. 7. These results suggest that the gastric mucosa of diabetic rats is more vulnerable to acid injury following barrier disruption, and this change is insulin-sensitive and may be partly accounted for by the impairment of GMBF response associated with acid back-diffusion and mediated by capsaicin-sensitive sensory neurons.
摘要
我们检测了糖尿病大鼠经牛磺胆酸钠（TC）诱导屏障破坏后的胃黏膜血流量（GMBF）和致溃疡反应，并研究了辣椒素敏感感觉神经元在这些反应中的作用。2. 动物腹腔注射链脲佐菌素（STZ：70 mg kg⁻¹），在糖尿病5、10和15周后使用，血糖水平> 350 mg dl⁻¹。在乌拉坦麻醉下将胃安装在离体腔室中，在奥美拉唑存在的情况下暴露于20 mM TC加50 mM HCl 30分钟。在暴露于20 mM TC之前和之后测量胃跨黏膜电位差（PD）、GMBF和腔内酸损失（H⁺反向扩散），并在TC处理90分钟后检查黏膜损伤情况。3. 黏膜应用TC导致所有组的PD降低；正常大鼠和糖尿病大鼠之间PD降低的程度相似，尽管糖尿病大鼠的基础PD值较低。在正常大鼠中，TC处理导致腔内酸损失，随后GMBF增加，导致黏膜损伤最小。4. 与H⁺反向扩散相关的GMBF增加反应在STZ处理的大鼠中减轻，这取决于糖尿病的持续时间，并且糖尿病10周后胃中出现严重的出血性病变。5. 胃内应用辣椒素可增加正常大鼠的GMBF，但在STZ糖尿病大鼠中这种反应减轻。与对照组相比，糖尿病大鼠离体胃中对辣椒素反应释放的降钙素基因相关肽（CGRP）量显著降低。6. 每日胰岛素（4单位大鼠⁻¹）治疗部分但显著地拮抗了STZ糖尿病大鼠对GMBF和黏膜致溃疡反应的有害影响。7. 这些结果表明，糖尿病大鼠的胃黏膜在屏障破坏后对酸损伤更敏感，这种变化对胰岛素敏感，并且可能部分是由与酸反向扩散相关的GMBF反应受损以及由辣椒素敏感感觉神经元介导的。
