Caniano D A, Grace G T, Sun C C, Ormsbee H S, Hardy F E, Hill J L
J Pediatr Surg. 1986 Dec;21(12):1128-32. doi: 10.1016/0022-3468(86)90024-2.
Diminished concentrations of the gut neuropeptide, vasoactive intestinal peptide (VIP), have been measured by radioimmunoassay in man and mouse models of Hirschsprung's disease. This in vitro study was designed to ascertain the functional response to VIP in aganglionic colon. Seven piebald lethal (PLM) mice with histologically verified aganglionosis and seven normal littermates (NLM) were sacrificed. Distal colonic segments were placed in standard oxygenated tissue baths and responses to electrical field stimulation (EFS), acetylcholine (ACh), and VIP recorded and analyzed by a motility index (MI). Aganglionic colonic tissues from PLM exhibited marked basal contractile activity in contrast to NLM (MI = 19.5 +/- 2.0 SEM v 6.5 +/- 3.6 SEM, P less than .01). In NLM tissues, VIP reduced the MI to ACh challenge by 49% (P less than .01), while in PLM tissues, a nonsignificant 22% reduction was observed. VIP blocked the response to EFS in NLM tissues, while no response was elicited to EFS in PLM tissues. An in vitro deficit in the VIP inhibitory response to ACh challenge is apparent in PLM with distal colonic aganglionosis. The increased basal activity and reduction in responsiveness to VIP, observed in the PLM tissues, support a generalized reduction in the function of the inhibitory innervation of the aganglionic colon.
在先天性巨结肠症的人类和小鼠模型中，已通过放射免疫测定法测量了肠道神经肽血管活性肠肽（VIP）浓度的降低情况。这项体外研究旨在确定无神经节结肠对VIP的功能反应。处死了7只经组织学证实患有无神经节症的花斑致死（PLM）小鼠和7只正常同窝仔鼠（NLM）。将远端结肠段置于标准的含氧组织浴中，并通过运动指数（MI）记录和分析对电场刺激（EFS）、乙酰胆碱（ACh）和VIP的反应。与NLM相比，PLM的无神经节结肠组织表现出明显的基础收缩活性（MI = 19.5 +/- 2.0 SEM对6.5 +/- 3.6 SEM，P <.01）。在NLM组织中，VIP使对ACh刺激的MI降低了49%（P <.01），而在PLM组织中，观察到降低了22%，但无统计学意义。VIP阻断了NLM组织对EFS的反应，而PLM组织对EFS无反应。在患有远端结肠无神经节症的PLM中，对ACh刺激的VIP抑制反应存在体外缺陷。在PLM组织中观察到的基础活性增加和对VIP反应性降低，支持了无神经节结肠抑制性神经支配功能普遍降低的观点。
