论文部分内容阅读
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。
Female patients during pregnancy and menstrual cycle luteal phase often abdominal pain, abdominal distension and diarrhea and other symptoms of gastrointestinal disorders. This study was designed to investigate the effects of estradiol benzoate (EB) and progesterone (P_4) on the plasma levels of cholecystokinin (CCK) and CCK_A in ovariectomized rats, In order to clarify the mechanism of ovarian hormones regulating gastrointestinal motility and sensory function. The ovariectomized rats were given EB and P_4 replacement therapy. The plasma concentrations of CCK and CGRP were determined by radioimmunoassay. The expression of CCK_A receptor in gastric tissues was detected by Western blot. The radioactive ligands of ~ (125) I-CGRP Binding assay was used to determine the expression of CGRP receptor in gastric tissue. EB can increase the concentration of plasma CCK, while causing CCK_A receptor expression in gastric tissue increased. P_4 had no significant effect on the concentration of CCK in plasma and the expression of CCK_A receptor in gastric tissue, but P_4 increased the concentration of plasma CGRP and upregulated the activity of CGRP in gastric tissue. EB and P_4 increased the levels of plasma CCK and CGRP, and increased the expression of CCK_A and CGRP receptors in the stomach. Therefore, EB can inhibit gastric emptying by promoting the secretion of CCK and upregulating the expression of CCK_A receptor in the stomach, while P_4 can increase the sensitivity of the enteric nervous system to external stimuli by increasing the release of CGRP and upregulating the activity of CGRP receptors in the stomach . The results suggest that CCK_A and CGRP receptor antagonists may be used to treat gastrointestinal disorders such as abdominal distension, early fullness and abdominal pain which are closely related to the menstrual cycle in female patients.