红霉素中枢拟胃动素作用及诱导室旁核c-Fos蛋白的表达

THE MOTILIN-LIKE EFFECT OF ERYTHROMYCIN IN CNS AND ITS EFFECT ON THE EXPRESSION OF c-Fos PROTEIN IN PARAVENTRICULAR NUCLEI

目的探讨红霉素（EM）在中枢的拟胃动素作用及其可能的机制。方法应用核团微量注射法,记录清醒大鼠胃运动,观察侧脑室分别注射生理盐水、不同剂量的EM（9.16、45.78、91.56nmol）及胃动素受体拮抗剂（91.56nmol EM＋2.95nmol GM109）后,对清醒自由活动大鼠胃运动的影响;应用免疫组织化学方法,观察侧脑室分别注射生理盐水、不同剂量的EM（45.78、91.56nmol）及胃动素受体拮抗剂（91.56nmol EM＋2.95nmolGM109）后,大鼠室旁核（PVN）内c-Fos蛋白的表达。结果与生理盐水组相比,侧脑室微量注射EM后,清醒大鼠胃运动增强,增强的幅度与EM呈剂量依赖性,其中45.78nmol EM组胃收缩幅度增加在5、10min时差异有显著性（F=32.14、36.24,q=3.46、2.14,P〈0.01）,91.56nmol EM组胃运动幅度增加在5、10、15、20min时差异有显著性（F=35.32-39.44,q=2.56-3.26,P〈0.01）,9.16nmol EM组胃运动变化均无统计学差异。GM109可以部分阻断91.56nmol EM的促胃运动作用。侧脑室微量注射不同剂量的EM可以诱导下丘脑室旁核神经元c-Fos蛋白的表达,具有剂量依赖性,2.95nmol GM109可以部分阻断91.56nmol EM诱导的下丘脑室旁核c-Fos蛋白的表达。生理盐水组只有极低水平的c-Fos的表达。结论EM侧脑室注射具有胃动素样的促进胃运动的作用,这种作用可能是通过中枢胃动素受体介导的;下丘脑室旁核可能是EM发挥中枢作用的作用部位之一。

Objective To study whether EM has a motilin-like effect on CNS and its possible mechanism. Methods Gastric motility was recorded in conscious rats after 1. C. V. microinjection of normal saline, different dosage of EM （9. 16 nmol, 45. 78 nmol, 91.56 nmol）, and EM 91.56 nmol＋GM109 2.95 nmol. The expression of c-Fos protein in the brain was detected with immunohistochemistry technique 90 minutes after injection of normal saline, EM（45. 78 nmol, 91.56 nmol）, or EM 91. 56 nmol＋ GM109 2.95 nmol into the lateral cerebroventricle. Results A dose-dependent motility-stimulating effect of EM on the gastric motor amplitude in conscious rats was observed, the difference of amplitude between the EM 45.78 nmol and NS were significant in 10 minutes after injection （F=32.14,36.24,q= 3.46,2.14,P〈0.01）. The difference of amplitude between the EM 91. 56 nmol and NSwere significant in 20 minutes after the injection （F=35.32-39.44,q= 2.56=3.26,P〈0.001）. GM109 2. 95 nmol can partially blocked the stimulating effect of EM 91.56 nmol on the gastric motor amplitude. I.C.V. injection of EM 45.78 nmol or EM 91.56 nmol induced the expression of c-Fos protein in PVN in a dose-dependent manner. GM109 2.95 nmol partially blocked the effect EM 91.56 nmol on c-Fos expression in PVN. Conclusion I. C. V. injection of EM has a motility-stimulating effect on gastric motor amplitude in conscious rats, which might be mediated by the central motilin receptor; I. C. V. injection of EM induces the expression of c-Fos protein in PVN, which indicates that one of the possible regions where EM exerts its motilin like effect is PVN.