小脑顶核微量注射蝇蕈醇加剧大鼠应激性胃黏膜损伤。
Muscimol microinjection into cerebellar fastigial nucleus exacerbates stress-induced gastric mucosal damage in rats.
机构信息
Department of Gastroenterology, Affiliated Hospital of Xuzhou Medical College, China.
出版信息
Acta Pharmacol Sin. 2013 Feb;34(2):205-13. doi: 10.1038/aps.2012.152. Epub 2012 Dec 17.
AIM
To investigate the effects of microinjection of the GABA(A) receptor agonist muscimol into cerebellar fastigial nucleus (FN) on stress-induced gastric mucosal damage and the underlying mechanism in rats.
METHODS
Stress-induced gastric mucosal damage was induced in adult male SD rats by restraining and immersing them in cold water for 3 h. GABA(A) receptor agonist or antagonist was microinjected into the lateral FN. The decussation of superior cerebellar peduncle (DSCP) was electrically destroyed and the lateral hypothalamic area (LHA) was chemically ablated by microinjection of kainic acid. The pathological changes in the gastric mucosa were evaluated using TUNEL staining, immunohistochemistry staining and Western blotting.
RESULTS
Microinjection of muscimol (1.25, 2.5, and 5.0 μg) into FN significantly exacerbated the stress-induced gastric mucosal damage in a dose-dependent manner, whereas microinjection of GABA(A) receptor antagonist bicuculline attenuated the damage. The intensifying effect of muscimol on gastric mucosal damage was abolished by electrical lesion of DSCP or chemical ablation of LHA performed 3 d before microinjection of muscimol. Microinjection of muscimol markedly increased the discharge frequency of the greater splanchnic nerve, significantly increased the gastric acid volume and acidity, and further reduced the gastric mucosal blood flow. In the gastric mucosa, further reduced proliferation cells, enhanced apoptosis, and decreased anti-oxidant levels were observed following microinjection of muscimol.
CONCLUSION
Cerebellar FN participates in the regulation of stress-induced gastric mucosal damage, and cerebello-hypothalamic circuits contribute to the process.
目的
研究小脑绒球核（FN）内微量注射 GABA(A) 受体激动剂 muscimol 对大鼠应激性胃黏膜损伤的影响及其机制。
方法
采用束缚浸水法制作成年雄性 SD 大鼠应激性胃黏膜损伤模型，将 GABA(A) 受体激动剂或拮抗剂微量注射到 FN 侧部，用电损毁小脑上脚交叉（DSCP），用微注射海人藻酸损毁外侧下丘脑区（LHA）。用 TUNEL 染色、免疫组织化学染色和 Western blot 检测胃黏膜的病理变化。
结果
FN 内微量注射 muscimol（1.25、2.5 和 5.0 μg）可显著加重应激性胃黏膜损伤，呈剂量依赖性，而 GABA(A) 受体拮抗剂 bicuculline 可减轻损伤。在 microinjection muscimol 前 3 天进行 DSCP 电损毁或 LHA 化学损毁，可消除 muscimol 对胃黏膜损伤的增强作用。微量注射 muscimol 可显著增加大内脏神经的放电频率，显著增加胃酸体积和酸度，进一步减少胃黏膜血流量。在胃黏膜中，注射 muscimol 后观察到增殖细胞减少、凋亡增加、抗氧化水平降低。
结论
小脑 FN 参与了应激性胃黏膜损伤的调节，而小脑-下丘脑环路参与了这一过程。
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