Choudhury Barun K, Shi Xuan-Zheng, Sarna Sushil K
Enteric Neuromuscular Disorders and Visceral Pain Center, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, 9.138 Medical Research Bldg., Galveston, TX 77555-1064, USA.
Am J Physiol Gastrointest Liver Physiol. 2009 Mar;296(3):G632-42. doi: 10.1152/ajpgi.90673.2008. Epub 2009 Jan 8.
The cellular mechanisms of motility dysfunction in postinfectious irritable bowel syndrome (PI-IBS) are not known. We used a rat model of neonatal inflammation to test the hypothesis that gene plasticity in colonic circular smooth muscle cells underlies motility dysfunction in PI-IBS. Mild/moderate or severe inflammation was induced in neonatal and adult rats. Experiments were performed in tissues obtained at 7 days (short term) and 6-8 wk (long term) after the induction of inflammation. Severe inflammation in neonatal rats induced persistent long-term smooth muscle hyperreactivity to acetylcholine (ACh), whereas that in adult rat caused smooth muscle hyporeactivity that showed partial recovery in the long term. Mild/moderate inflammation had no effect in neonatal rats, but it induced smooth muscle hyporeactivity to ACh in adult rats, which recovered fully in the long term. Smooth muscle hyperreactivity to ACh resulted in accelerated colonic transit and increase in defecation rate, whereas hyporeactivity had opposite effects. Smooth muscle hyperreactivity to ACh was associated with increase in transcription rate of key cell-signaling proteins of the excitation-contraction coupling alpha1C subunit of Cav1.2 (L-type) calcium channels, Galphaq, and 20-kDa myosin light chain (MLC20), whereas hyporeactivity was associated with their suppression. Inflammation in adult rats induced classical inflammatory response, which was absent in neonatal rats. Severe neonatal inflammation enhanced plasma norepinephrine and muscularis propria vasoactive intestinal polypeptide in the long term. We conclude that severe, but not mild/moderate, inflammation in a state of immature or impaired stress and immune response systems alters the transcription rate of key cell-signaling proteins of excitation-contraction coupling in colonic circular smooth muscle cells to enhance their contractility and accelerate colonic transit and defecation rate.
感染后肠易激综合征（PI-IBS）中运动功能障碍的细胞机制尚不清楚。我们使用新生大鼠炎症模型来检验以下假设：结肠环行平滑肌细胞中的基因可塑性是PI-IBS运动功能障碍的基础。在新生和成年大鼠中诱导轻度/中度或重度炎症。在炎症诱导后7天（短期）和6 - 8周（长期）获得的组织中进行实验。新生大鼠的重度炎症诱导了对乙酰胆碱（ACh）持续的长期平滑肌高反应性，而成年大鼠的重度炎症则导致平滑肌低反应性，且在长期中表现出部分恢复。轻度/中度炎症对新生大鼠没有影响，但在成年大鼠中诱导了对ACh的平滑肌低反应性，且在长期中完全恢复。对ACh的平滑肌高反应性导致结肠转运加速和排便率增加，而低反应性则产生相反的效果。对ACh的平滑肌高反应性与兴奋 - 收缩偶联关键细胞信号蛋白Cav1.2（L型）钙通道的α1C亚基、Gαq和20 kDa肌球蛋白轻链（MLC20）的转录速率增加有关，而低反应性则与它们的抑制有关。成年大鼠的炎症诱导了经典的炎症反应，新生大鼠中则不存在这种反应。长期来看，重度新生炎症增强了血浆去甲肾上腺素和肌层血管活性肠肽。我们得出结论，在未成熟或受损的应激和免疫反应系统状态下，重度而非轻度/中度炎症会改变结肠环行平滑肌细胞中兴奋 - 收缩偶联关键细胞信号蛋白的转录速率，以增强其收缩性并加速结肠转运和排便率。
