早期母婴分离对成年大鼠内脏感觉和肠道炎症的影响

摘要

心理-社会因素在肠易激综合征(IBS)的发病机制中起重要作用,但早期生活事件如母婴分离对内脏敏感性的负性影响尚存在争议.目的:探讨早期母婴分离对成年大鼠内脏感觉和肠道黏膜炎症的影响.方法:37只新生雄性Sprague-Dawley幼鼠随机分为正常对照组、母婴分离组、急性避水应激组.母婴分离组幼鼠出生第2d开始进行母婴分离,持续至出生后第3周.2月龄时大鼠接受结肠气囊扩张,行腹壁回撤反射(AWR)评分和腹壁肌电测定；观察结肠组织病理学变化,以甲苯胺蓝染色法测定肥大细胞(MC)计数和脱颗粒率；以ELISA法测定结肠组织IL-1β和类胰蛋白酶含量.结果:母婴分离组结肠组织学评分、MC计数、IL-1β和类胰蛋白酶含量均显著高于避水应激组、正常对照组(P＜0.05).当结肠内气囊压力为40、60、80 mm Hg时,母婴分离组和避水应激组AWR评分和腹壁肌电幅值均显著高于正常对照组(P＜0.05),且母婴分离组AWR评分和腹壁肌电幅值与上述各项炎症指标均呈正相关(P＜0.05).结论:早期母婴分离和急性避水应激均可导致内脏感觉过敏,早期母婴分离还可诱导肠道黏膜低度炎症,这种低度炎症可能与内脏感觉过敏相关.%Background; Social and psychological factors play important roles in the pathogenesis of irritable bowel syndrome (IBS). However, it remains a controversy that early life events (such as maternal separation) have negative effects on the visceral sensitivity. Aims; To evaluate the role of neonatal maternal separation on visceral sensitivity and intestinal mucosal inflammation in adult rats. Methods; Thirty-seven newborn male Sprague-Dawley rats were randomly divided into control group, maternal separation group and acute water avoidance group. The newborn male rats in maternal separation group received maternal separation between the 2nd-21st day postnatally. At the 2nd month, abdominal withdrawal reflex (AWR) score and myoelectric amplitude of the oblique externus abdominis muscle were recorded after colonic balloon distention. Histopathological changes were observed, toluidine blue stain was used to determine mast cell (MC) count and degranulation, and the contents of IL-1β and tryptase in colon were detected by ELISA. Results; The histological score, MC count, contents of IL-lβ and tryptase in maternal separation group were significantly higher than those in water avoidance group and control group (P<0.05). When the balloon pressure was set to 40, 60, 80 mm Hg, respectively, AWR score and myoelectric amplitude in maternal separation group and water avoidance group were significantly higher than those in control group ( P < 0. 05 ). AWR score and myoelectric amplitude in maternal separation group were positively correlated with the above-mentioned mucosal inflammation indices (P < 0.05). Conclusions; Neonatal maternal separation and acute water avoidance activate visceral hypersensitivity. Maternal separation also induces low-grade mucosal inflammation in colon, which may be involved in the pathogenesis of visceral hypersensitivity in adult rats.