Expression of motilin in the hypothalamus and the effect of central eryth-romycin on gastric motility in diabetic rats

糖尿病大鼠下丘脑中胃动素的表达及中枢注射红霉素对胃运动的影响

Objective To investigate the expression of motilin-immunoreactive neurons in the hypothalamus and the effect of central administration of erythromycin （EM） on the regulation of gastric motility in diabetic rats. Methods The motilin immunoreactive neurons in the hypothalamus and the hippocampus were detected by immunohistochemistry with rabbit anti-motilin polyclonal antibody. To measure the gastric motility, force transducers were surgically affixed to the gastric serosa. A microinjection syringe was connected via a plastic tube to an injection cannula, which was connected with a stainless steel guide cannula. The syringe was inserted into the right lateral cerebral ventricle for microinjecting the chemicals. Results Diabetic mellitus was successfully induced in cohorts of rats. Motilin-immunoreactive neurons significantly increased in the paraventricular （PVN） and supraoptic nuclei （SON） of the hypothalamus in the diabetic rats. Intracerebroventricular （i.c.v.） administration of EM, a motilin receptor agonist, stimulated the gastric motility of diabetic rats. EM （91.56 nmol, i.c.v.） dose-dependently increased the amplitude by （174.82±48.62）% （P 〈 0.05）, and increased the frequency by （70.43±27.11）% （P 〈 0.05） in 5 min. The stimulatory effect lasted more than 15 min to the end of the measurement, and can be blocked partially by the prior treatment of motilin receptor antagonist GM-109. Conclusion Motilin-immunoreactive neurons are increased in the PVN and SON of the hypothalamus in diabetic rats. Centrally administered EM may regulate gastric motility by binding to the central motilin receptors, and central motilin might be involved in regulation of gastric motility in diabetic rats.

目的以往的研究表明胃动素存在于大鼠的中枢神经系统,在中枢注射胃动素具有促进清醒大鼠胃运动的作用。但糖尿病大鼠中枢胃动素表达含量及中枢注射胃动素对糖尿病大鼠胃运动的潜在作用目前尚未报导。本研究探索糖尿病大鼠胃动素免疫阳性神经元在下丘脑的表达,观察侧脑室微量注射胃动素受体激动剂红霉素(erythromycin, EM)对正常和糖尿病大鼠胃运动的作用。方法采用免疫组织化学方法测定下丘脑胃动素免疫阳性神经元的分布特征。在胃窦浆膜层植入应力传感器,测定清醒大鼠胃运动的幅度和频率。结果糖尿病大鼠下丘脑室旁核和视上核胃动素免疫阳性神经元数量明显高于正常对照大鼠(P<0.05)。脑室内微量注射EM可以明显促进糖尿病大鼠的胃运动。注射91.56nmol的EM五分钟后,大鼠胃窦运动幅度升高(174.82±48.62)%(P<0.05),运动频率加快(70.43±27.11)% (P<0.05)。在脑室内微量注射胃动素拮抗剂GM-109后,再注射EM, 其促胃运动效应可被部分阻断。结论糖尿病大鼠中枢胃动素对胃运动有一定的调制作用,而且脑室内微量注射的EM是通过脑内的胃动素受体介导而发挥其促胃动力效应。