卵巢激素调节大鼠胃运动及感觉功能的机制(英文)  

Regulative effects of ovarian steroids on rat gastric motility and sensitivity

作　　者：杨霞[1] 刘然[1] 董艳[1] 

机构地区：[1]山东大学齐鲁医院,济南250012

出　　处：《生理学报》2006年第3期275-280,共6页Acta Physiologica Sinica

基　　金：This work was supported by a research grant from Chinese Development Foundation of Taiwan in 2004.

摘　　要：女性患者在孕期及月经周期的黄体期常有腹痛、腹胀及腹泻等胃肠道功能紊乱的症状。本文探讨雌二醇(estradiol benzoate,EB)和孕酮(progesterone,P_4)对卵巢切除大鼠血浆胆囊收缩素(cholecystokinin,CCK)及胃组织内胆囊收缩素受体A(CCK_A)、血浆降钙素基因相关肽(calcitonin gene-related peptide,CGRP)及胃组织内其受体表达水平的影响,以期阐明卵巢激素调节胃肠道运动及感觉功能的机制。给予卵巢切除大鼠EB和P_4替代治疗,用放射免疫分析法测定血浆CCK、CGRP的浓度,用Western blot法检测胃组织内CCK_A受体的表达量,用^(125)I-CGRP放射配体结合分析法测定胃组织内CGRP受体的表达量。EB可以升高血浆CCK的浓度,同时引起胃组织内CCK_A受体表达增高。P_4对血浆CCK的浓度以及胃组织内CCK_A受体的表达无明显影响,但P_4可以升高血浆CGRP的浓度,上调胃组织内CGRP受体的活性。EB、P_4联合作用升高血浆CCK、CGRP的浓度,增加胃内CCK_A、CGRP受体的表达。因此EB通过促进CCK的分泌以及上调胃内CCK_A受体的表达,抑制胃排空；而P_4可以通过增加CGRP的释放上调胃内CGRP受体的活性,从而增加肠神经系统对外来刺激的敏感性。结果提示,可以利用CCK_A、CGRP受体的拮抗剂治疗女性患者中与月经周期有密切关系的胃肠道功能紊乱症状,如腹胀、早饱、腹痛等。Women often complain gut symptoms during pregnancy and the luteal phase of the menstrual cycle. To investigate the relationship between ovarian steroids and the abnormal gut motility and sensitivity, the expressions of cholecystokinin （CCK）,calcitonin gene-related peptide （CGRP） and their receptors in stomach were studied in ovariectomized rats. Blood samples were collected for estradiol （E2）, progesterone （P4）, CCK and CGRP radioimmunoassay. Expression of CCKA receptor in fundus was assessed by Western blot and CGRP receptor was determined by 125I-CGRP radioligand binding assay （RBA）. The replacement therapy with estradiol benzoate （EB） could dose-dependently increase the plasma CCK level and the expression of gastric CCKA receptor （P＜0.05 respectively）. P4 replacement therapy could stimulate the release of CGRP and increase the binding sites of CGRP receptors in stomach （P＜0.05 respectively）. The combined effect of EB and P4 was to stimulate the release of CCK and CGRP, and to increase the expressions of gastric CCKA and CGRP receptors. These results indicate that EB could inhibit gastric emptying by increasing CCK secretion and CCKA receptor expression in ovariectomized rats. P4 could increase gut sensitivity by up-regulating the release of CGRP and the activity of CGRP receptor. It could be deduced from these observations that CCKA and CGRP receptor antagonists could be used for female patients who suffer from gastrointestinal dysfunction closely related with the menstrual cycle,such as distension, satiety, bloating and abdominal pain.

关 键 词：雌二醇 孕酮 受体 胆囊收缩素 降钙素基因相关肽 

分 类 号：R339[医药卫生—人体生理学]