血红素氧合酶与 Cajal 间质细胞在糖尿病大鼠结肠动力障碍中的作用

背景: 血红素氧合酶(HO)催化生成的内源性CO为抑制性神经递质,HO与Cajal间质细胞(ICC)间的相互作用在糖尿病(DM)胃肠动力障碍的研究中备受关注。目的: 探讨HO和ICC在DM大鼠结肠动力障碍中的作用以及其间的关系。方法: 建立DM大鼠结肠慢传输型动力障碍模型,6周后随机分为不予干预的DM组、DM+氯化高铁血红素(Hemin,HO诱导剂)组和DM+锌原卟啉(ZnPP,HO阻滞剂)组,每组8只。9周末测定胃肠推进指数,以蛋白质印迹法检测结肠HO-1、HO-2、c-kit表达情况,间接双重免疫荧光法检测c-kit与HO-1、HO-2共表达情况。结果: DM+Hemin组胃肠推进指数较DM组显著降低,DM+ZnPP组则较DM组显著增高(P均0.05)。正常对照组与DM组近、远端结肠HO-1表达无明显差异,DM+Hemin组较该两组显著增高(P0.05),DM+ZnPP组基本不表达HO-1。DM组、DM+Hemin组和DM+ZnPP组间近端结肠HO-2表达无明显差异,均显著低于正常对照组(P0.05),四组间远端结肠HO-2表达无明显差异。DM组近、远端结肠c-kit表达较正常对照组显著降低(P0.05),DM+Hemin组略低于DM组,DM+ZnPP组较DM组显著增高(P0.05)。除DM+ZnPP组基本不存在c-kit与HO-1共表达外,四组均存在c-kit与HO-1、HO-2共表达,以肌间神经丛区域为著。结论: 结肠ICC减少伴HO表达变化可能是DM大鼠结肠慢传输型动力障碍的机制之一。

Role of Heme Oxygenase and Interstitial Cells of Cajal in Colonic Dysmotility of Diabetic Rats

Endogenous carbon monoxide （CO）, which is catalyzed by heme oxygenase （HO）, has been suggested to be an inhibitory neurotransmitter. The relationship between HO and interstitial cells of Cajal （ICC） has been concerned in researches of gastrointestinal dysmotility in diabetes mellitus （DM）. Aims： To investigate the effects and relationship of HO and ICC on colonic dysmotility in DM rats. Methods： DM model with colonic slow-transit dysmotility in rats were established. Six weeks later, the DM rats were randomized into DM group without intervention, DM＋Hemin （inducer of HO） group and DM＋ZnPP （inhibitor of HO） group, eight rats were in each group. Nine weeks later, GI propulsion rate was tested, expressions of HO-1, HO-2 and c-kit in colonic tissue were detected by Western blotting, and co-express/on of c- kit with HO-1/HO-2 was measured by indirect double-labelling immunofluorescence. Results： The GI propulsion rate of DM＋Hemin group was significantly decreased compared to that of the DM group, while that of the DM＋ZnPP group was significantly increased compared to the DM group （both P〈0.05）. There was no significant difference on the expression of HO-1 in proximal and distal colon between the controls and the DM group, while that of the DM＋Hemin group was much higher （P〈0.05）, and the DM＋ZnPP group almost with no expression. There was no significant difference on the expression of HO-2 in proximal colon between DM group, DM＋Hemin group and DM＋ZnPP group, all were lower than that of the controls （P〈0.05）. There was no significant difference on the expression of HO-2 in distal colon among the four groups. The expression of c-kit in proximal and distal colon of the DM group was significantly decreased than that of the controls （P〈 0.05）, while that of the DM＋Hemin group was slightly lower and that of the DM＋ZnPP group was significantly higher （P〈 0.05）. All the groups displayed co-expression of c-kit and HO-1/HO-2, especially in myenteric nerve plexus, except for the DM＋ZnPP group, with almost no co-expression of c-kit and HO-1. Conclusions： Decreased number of ICC and changeable expression of HO in colonic tissue might be one of the mechanisms in colonic slow-transit dysmotility in DM rats.