Xiao Zuo-Liang, Pricolo Victor, Biancani Piero, Behar Jose
Department of Medicine, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island 02903, USA.
Gastroenterology. 2005 Mar;128(3):667-75. doi: 10.1053/j.gastro.2004.12.001.
BACKGROUND & AIMS: Chronic constipation caused by slow transit is common in women with an F/M ratio of 9:1. The cause and mechanisms responsible for this syndrome are unknown. Progesterone has been suggested as a possible contributing factor. Our aim was to investigate the site and mechanisms responsible for this colonic motility disorder.
Seven women with intractable constipation and slow transit time underwent colectomy and 6 women who underwent a left colectomy for adenocarcinoma (controls) were studied. Dissociated colonic circular muscle cells were obtained by enzymatic digestion. Changes in G-protein levels were measured by Western blot. The messenger RNA (mRNA) expression of Galpha q and progesterone receptors was determined by reverse-transcription polymerase chain reaction and Northern blot.
Muscle cells from patients with chronic constipation exhibited impaired contraction in response to receptor-G-protein-dependent agonists (cholecystokinin [CCK], acetylcholine) and in response to the direct G-protein activator guanosine 5'-O-(3-thiophosphate). Contraction was normal with receptor-G-protein-independent agonists (diacylglycerol and KCl). Western blot showed down-regulation of Galpha q/11 and up-regulation of Galpha s proteins in patients with chronic constipation. The mRNA expression of Galpha q was lower and the progesterone receptors were overexpressed in patients with chronic constipation compared with controls. These abnormalities were reproduced in vitro by pretreatment of normal colonic muscle cells with progesterone for 4 hours.
Slow transit chronic constipation in women may be caused by down-regulation of contractile G proteins and up-regulation of inhibitory G proteins, probably caused by overexpression of progesterone receptors.
慢传输型慢性便秘在女性中很常见，男女比例为9:1。该综合征的病因及机制尚不清楚。有人提出孕酮可能是一个促成因素。我们的目的是研究这种结肠动力障碍的部位及机制。
对7例顽固性便秘且传输时间缓慢的女性进行结肠切除术，并对6例因腺癌接受左半结肠切除术的女性（对照组）进行研究。通过酶消化获得解离的结肠环行肌细胞。用蛋白质免疫印迹法检测G蛋白水平的变化。通过逆转录聚合酶链反应和Northern印迹法测定Gαq和孕酮受体的信使核糖核酸（mRNA）表达。
慢性便秘患者的肌细胞对受体-G蛋白依赖性激动剂（胆囊收缩素[CCK]、乙酰胆碱）以及直接G蛋白激活剂鸟苷5'-O-（3-硫代磷酸酯）的反应性收缩受损。对受体-G蛋白非依赖性激动剂（二酰甘油和氯化钾）的收缩反应正常。蛋白质免疫印迹法显示，慢性便秘患者中Gαq/11下调，Gαs蛋白上调。与对照组相比，慢性便秘患者中Gαq的mRNA表达较低，孕酮受体过度表达。用孕酮对正常结肠肌细胞预处理4小时后，体外实验再现了这些异常情况。
女性慢传输型慢性便秘可能是由收缩性G蛋白下调和抑制性G蛋白上调引起的，这可能是由于孕酮受体过度表达所致。
