一氧化氮能神经调节异常在腹泻型肠易激综合征患者中的作用

目的　探讨一氧化氮 (NO)在肠易激综合征 (IBS)发病机制中的作用 ,并从基因水平揭示NO含量改变的原因。方法　 (1)应用电子气压泵及灌注导管测压仪研究 2 5例腹泻型IBS患者及 15例正常志愿者的肛门、直肠压力、直肠顺应性、乙状结肠和直肠运动指数以及直肠对容量刺激的感觉阈值 ;(2 )应用硝酸还原酶法测定两组肠黏膜NO的含量 ;(3)NADPH黄递酶组化法和计算机图像分析系统对两组肠黏膜肌层一氧化氮合酶 (NOS)阳性神经纤维作定量分析 ;(4)采用荧光定量PCR(FQ PCR)方法对神经型一氧化氮合酶 (nNOS)的基因表达进行定量分析。结果　 (1)肠道测压 :IBS患者的直肠静息压、肛管上部静息压、收缩压、松弛压、肛管下部静息压、收缩压、松弛压和直肠顺应性与正常人比较 ,差异无显著性 (P >0 .0 5 ) ;患者乙状结肠和直肠运动指数明显高于正常人 (P <0 .0 5 ) ;(2 )直肠内脏感觉阈值 :最低感觉阈值、排便阈值和疼痛阈值明显低于正常人 (P <0 .0 5 ) ;(3)肠黏膜NO含量 :患者结肠黏膜NO含量显著低于正常人 ,并且患者的NO含量与运动指数成负相关 ,与感觉阈值、排便阈值、疼痛阈值呈正相关 (P <0 .0 5 ) ;(4)NADPH组化染色 :IBS患者黏膜肌层NOS阳性神经纤维的面积和平均吸光度较正常人显著减少 (P <0 .0 5 ) ;(5 )NOS mRNA

The role of Nnos-Mrna expression in patients with diarrhea predominant IBS

Objective To investigate the possible role of mRNA expression of nitric oxide synthase in the abnormal intestinal motility and visceral perception in patients with diarrhea predominant IBS. Methods Anorectal manometry and rectal visceral sensory thresholds were examined in 25 patients with diarrhea predominant IBS and 15 healthy controls by means of electric barostat and perfusion catheter manometer. The quantity of NO was measured using nitrate/nitrite colorimetric assay. The nerve fibers containing NOS in mucosal muscular layer of colon was quantitatively measured with NADPH diaphorase histochemistry assay and computer image analysis. The expression of neuronal nitric oxide synthase (nNOS) mRNA was determined with fluorescence quantitative polymerase chain reaction (FQ PCR). Results Thresholds of first perception, defecation and pain in patients with IBS were significantly lower than those of controls. The motility indexes of sigmoid and rectum were significantly higher than those of normal controls ( P <0.05). The content of NO in colonic mucosa of patients with IBS was significantly lower than that of normal controls and showed negative correlation with visceral perception thresholds. The NOS containing nerve fibers in mucosal muscular layer of patients with IBS was significantly less than those of normal controls. nNOS mRNA expression was significantly lower in patients with IBS than in normal controls. Conclusions The reduction of nNOS mRNA expression in colonic mucosa may play a major role in the abnormal intestinal motility and visceral hypersensitivity of IBS.