血红素氧合酶2在吗啡诱导的结肠慢传输型便秘小鼠结肠中的表达及意义

Expression of heme oxygenase-2 in mouse model of colon slow transit motility constipation induced by morphine and its significance

目的:探讨血红素氧合酶2(HO-2)在吗啡诱导的结肠慢传输运动小鼠近端结肠组织中的表达,和其在慢传输型便秘发生发展中的作用.方法:将48只小鼠随机分为实验组A,实验组B和对照组,每组16只.实验组小鼠sc不同剂量吗啡,实验组A:2.5 mg/(kg·d)和实验组B:3.5 mg/(kg·d),共45 d,建立肠道慢传输运动小鼠模型,对照组以等量生理盐水处理:45 d后各组小鼠随机处死一半.剩余小鼠分别对应作为实验组A2,实验组B2和对照组2,不作处理观察15 d,再全部处死.用免疫组化技术比较各组小鼠近端结肠组织中HO-2阳性细胞的表达情况.结果:在实验组和对照组小鼠结肠组织中HO-2均有表达;实验组较正常组表达显著减少;实验组B较实验组A的表达明显减少;停用吗啡观察15 d后各实验组较45 d时各实验组表达明显减少.结论:吗啡诱导的肠道慢传输运动小鼠结肠组织中HO-2表达显著减少,并与吗啡剂量和时间有关,提示抑制性神经递质CO异常减少可能是肠道慢传输运动的病因之一.

AIM： To study the expression and changes of heme oxygenase-2 （HO-2） in a mouse model of morphine induced colon slow transit motility and the role of HO-2 in the development of slow transit motility constipation. METHODS： Forty-eight mice were randomly divided into test A group （n = 16）, test B group （n = 16） and control 1 group. A mouse model was established by subcutaneous injection of morphine [2.5 mg/（kg·d） in test Al and 3.5 mg/（kg·d） in test B1] for 45 days, and the control group 1 was established by normal saline injection at the same dosage. On the 45^th day, 8 mice from each group were killed. The remaining as test A2, test B2 and control group 2 mice received no treatment and were observed for 15 days, and then killed. The intestinal transit rate for mice in each group was detected by activated charcoal suspension pushing test, and the expression of HO-2^＊ cells in proximal colon tissue was determined by immunohistochemistry. RESULTS： The intestinal transit rate was decreased obviously in all test groups than in the control group, which was lower in test B than in test A. The intestinal transit rate for all test groups was significantly lower 15 days after colon slow transit motility constipation induced by morphine than 45 days before colon slow transit motility constipation induced by morphine. CONCLUSION： The c-kit^＊ cells are more obviously decreased in mouse proximal colon tissue with slow-transit motility constipation induced by morphine, and correlated with the dose and time of morphine used, suggesting that changes in nerve transmitter CO are one of the factors for colon slow-transit motility constipation.