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卵巢激素调节大鼠胃运动及感觉功能的机制

杨霞, 刘然, 董艳

山东大学齐鲁医院.山东,济南 250012

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。该文探讨雌二醇(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。

关键词： 雌二醇; 孕酮; 受体; 胆囊收缩素; 降钙素基因相关肽

Regulative effects of ovarian steroids on rat gastric motility and sensitivity

Yang Xia, Liu Ran, Dong Yan

Qilu Hospital, Shandong University.Jinan 250012,Shandong

Abstract

Women often complain more gut symptoms during pregnancy and the luteal phase of the menstrual cycle. To investigate the relationship of ovary steroids with the abnormal gut motility and sensitivity, the expression of cholecystokinin (CCK), calcitonin gene-related peptide (CGRP) and their receptors in rat stomach were studied in ovariectomized rats. Blood samples were collected for estradiol (E_(2)), progesterone (P_(4)), CCK and CGRP radioimmunoassay; Expression of CCK_(A) receptor in fundus was assessed by Western blotting and CGRP receptor was determined by ~(125)I-CGRP radioligand binding assay (RBA). The replacement therapy with estradiol benzote (EB) could dose-dependently increase the plasma CCK level and the expression of gastric CCK_(A) receptor (P<0.05 respectively). P_(4) 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 P_(4) was to stimulate the release of CCK and CGRP, increase the expression of gastric CCK_(A) and CGRP receptors. These results indicated that EB could inhibit gastric emptying by increasing CCK secretion and CCK_(A) receptor expression in ovariectomized rats. P_(4) 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 CCK_(A) 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.

Key words: Estradiol;Progesterone;Receptor;Cholecystokinin;calcitonin gene-related peptide

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引用本文：

杨霞, 刘然, 董艳. 卵巢激素调节大鼠胃运动及感觉功能的机制[J]. 生理学报 2006; 58 (3): .

Yang Xia, Liu Ran, Dong Yan. Regulative effects of ovarian steroids on rat gastric motility and sensitivity. Acta Physiol Sin 2006; 58 (3): (in Chinese with English abstract).