摘要
目的观察多潘立酮对食管和下食管括约肌（LES）的促动力作用，并与莫沙必利及西沙必利比较。方法在体实验：将40只大鼠分为对照组、多潘立酮组、莫沙必利组和西沙必利组。在各组大鼠近端食管体、远端食管体和LES埋植应力传感器，记录清醒大鼠食管体和LES运动。离体实验：在恒温灌流肌槽中，采用张力传感器测定多潘立酮、莫沙必利、西沙必利对大鼠离体食管体及LES肌条的收缩活动。结果在体实验：①清醒大鼠在消化间期的静息状态下，食管体呈现轻微的收缩运动。LES则出现典型的消化间期移行性复合运动（MMC）Ⅰ、Ⅱ、Ⅲ、Ⅳ相，其收缩强度大于食管体。②多潘立酮可明显增加食管体及LES的收缩运动，使近端食管体与远端食管体及LES平均振幅分别比对照组增加63．24％±7．17％，75．54％±5．27％和85．81％±6．02％，并呈剂量-效应关系。同等剂量的莫沙必利对近端食管体和远端食管体及LES平均振幅分别比对照组增加29．71％±4．15％，40．15％±3．30％和35．24％±5．36％。莫沙必利对食管和LES的促动力作用大大低于多潘立酮。而同等剂量的西沙必利对近端食管体和远端食管体及LES平均振幅分别比对照组增加59．84％±6．55％，70．11％±5．62％，75．13％士5．10％，其促动力作用与多潘立酮相同。离体实验：①灌流多潘立酮可明显刺激离体食管体肌条和LES肌条收缩，分别较Krebs—Ringer液对照组增加87．74％±7．65％和92．44％±7．17％。同等剂量的莫沙必利平均振幅分别较对照组Krebs—Ringer液增加35．42％±5．02％和31．12％±4．32％。莫沙必利的促动力作用大大低于多潘立酮。而同等剂量的西沙必利对离体食管和LES促动力作用与多潘立酮相同。②阿托品与河豚毒素均可阻断多潘立酮刺激食管及LES的动力作用。结论多潘立酮可明显刺激食管体收缩及明显增强LES动力，上述作用均明显优于莫沙必利并与西沙必利作用相同。多潘立酮增强食管与LES动力的作用机制，除已知阻断多巴胺受体外，还可能通过肠神经系统内胆碱能神经介导。
Objective To observe the prokinetic effect of domperidone on esophagus and lower esophageal sphincter （LES）, and compare its effect with that of mosapride and cisapride. Methods In vivo experiments： forty rats were divided into control, domperidone, mosapride, and cisapride groups. Strain gauges were planted in proximal esophagus, distal esophagus and LES to record the activities of esophagus and LES in conscious rat. In vitro experiments： in the thermostatic muscle bath, the prokinetic effect of domperidone, mosapride, and cisapride on the contractility of rat muscle strips from esophagus body and LES were recorded by tone-transducers. Results In vivo experiments： ① In the interdigestive period of resting conscious rats, only mild contraction activities were recoded in esophagus bodies. In LES, typical interdigestive migrating motor complex （MMC） with phase Ⅰ, Ⅱ, Ⅲ, and Ⅳ was recorded. The contraction amplitude of LES was much greater than esophagus body. ② Domperidone significantly enhanced the contraction of esophagus body and LES. The mean contraction amplitude of proximal esophagus, distal esophagus, and LES increased by 63.24%± 7.17 %, 75.54% ± 5.27 %, and 85.81% ± 6. 02%, respectively, compared with controls. The prokinetic effect showed a dose-effect relation. Mosapride at the same dosage increased the mean contraction amplitude of proximal esophagus, distal esophagus, and LES by 29. 71% ± 4. 15%, 40. 15% ± 3. 30%, and 35. 24% ± 5. 36%, respectively, compared with controls. The prokinetic effects of mosapride on esophagus and LES were much less than domperidone. Cisapride at the same dosage increased the mean contraction amplitude of proximal esophagus, distal esophagus, and LES by 59.84%±6.55%, 70.11%±5. 62%, and 75.13%± 5. 10%, respectively, compared with controls. The prokinetic effects of cisapride were similar as domperidone. In vitro experiments： ① Domperidone perfusion could significantly increase the contraction of esophagus body and LES muscle strips by 87. 74% ± 7. 65% and 92. 44% ± 7. 17%, respectively, compared with Krebs-Ringer （KR） solution perfuslon. Mosapride at the same dosage increased the mean contraction amplitude by 35. 42% ± 5. 02% and 31. 12%±4. 32%, respectively, compared with KR controls. The prokinetic effects of mosapride were much less than domperidone. Cisapride of the same dosage showed a similar prokinetic effect as domperidone. ② Atropine and tetrodotoxin could block the prokinetie effects of domperidone on esophagus and LES. Conclusions Domperidone can significantly enhance the esophagus body contraction and LES motility. The effects of domperidone are similar as cisapride and much greater than mosapride. The prokinetic effects of domperidone on esophagus and LES are not only through well-known dopaminergic receptor blockade, but also through the cholinergic nerves of the enteric nervous system.
出处
《中华消化杂志》
CAS
CSCD
北大核心
2008年第9期594-599,共6页
Chinese Journal of Digestion
