中枢及外周M胆碱受体在溃疡性结肠炎中对胆碱能抗炎通路的影响  

Effects of Central and Peripheral Muscarine Ach Receptors on Cholinergic Anti-inflammatory Pathway in the Model of Ulcerative Colitis

作　　者：梁天文[1] 余剑平[1] 王省[1] 孙燕玲[1] 潘锐[1] 张玲[1] 谢海琴[1] 陈健文[2] 

机构地区：[1]中山大学中山医学院实验教学中心,广东广州510080 [2]中山大学药学院,广东广州510080

出　　处：《深圳中西医结合杂志》2008年第6期340-344,共5页Shenzhen Journal of Integrated Traditional Chinese and Western Medicine

基　　金：广东省重点攻关基金(2003C30113);中山大学实验室开放基金项目资助(KF2008)

摘　　要：目的:从组织与器官水平探讨中枢及外周的M胆碱受体的激动剂与抑制剂引发的迷走神经传出的增加和减少,对胆碱能抗炎通路在溃疡性结肠炎抗炎作用的影响。方法:通过直肠插管灌注乙酸造成大鼠溃疡性结肠炎模型,分别从侧脑室微注射和腹腔注射毛果芸香碱、阿托品,观察其通过胆碱能抗炎通路对疾病活动指数(DAI)、组织学损伤(HI)、组织病理改变的影响。结果:脑室注射毛果芸香碱组大鼠DAI明显减小、结肠HI明显减轻(与模型组比P<0.05),病理观察可见结肠黏膜完好,炎症细胞浸润明显较模型组少;脑室注射阿托品组大鼠各指标则有加重的趋势,其它各组与模型组比较则无明显差异。结论:提示侧脑室注射M受体激动剂毛果芸香碱具有显著的治疗溃疡性结肠炎的作用,而侧脑室注射阿托品则具有一定促进炎症发展的作用,而对于外周给予M受体的激动剂和抑制剂均未表现出对外周组织炎症减轻或加重的明显影响。Objective Efferent activity in the vagus nerve can prevent and relieve wide-ranged inflammatory responsiveness in rodents through the ＂Cholinergic Anti-inflammatory Pathway＂ . The objective of our study is to investigate the effects of central and peripheral muscarine ACh receptors （mAChRs） on cholinergic anti-inflammatory pathway through activation and deactivation of mAChRs in level of tissues and organs. Methods The ulcerative colitis model of rats was made by injecting acetic acid through rectal cannula.Then mAChRs agonist （pilocarpine） and antagonist （atropine） were given to the rats through right intracerebroventricular （i.c.v） administration and intraperitoneal administration respectively. Control groups were set at the same time. Finally, development of inflammation in all the rats was assessed by disease active index （DAI）, histological index （HI） and pathological section index. Results DAI and colon HI reduced significantly in rats of pilocarpine group compared with those of model group （P 〈 0.05）. Pathological result showed colon mucosa was intact and inflammation cell number of pilocarpine group decreased significantly than that of model group. All parameters worsened in atropine group. There was no significant difference between model and other groups. Conclusion It was indicated that i.c.v pilocarpine treated group presented a marked decrease in the indexes of inflammation compared with acetic acid control, while a notable increase was recorded in the i.c.v atropine group. No significant differences were found in groups given drugs by intraperitoneal administration. Together, these results indicate that central activation of mAChRs can attenuate the inflammatory responsiveness, and central deactivation of mAChRs can promote the inflammatory responsiveness; while, peripheral mAChRs may not required for intact activity of the cholinergic anti-inflammatory pathway.

关 键 词：胆碱能抗炎通路 M胆碱受体 溃疡性结肠炎 侧脑室注射 

分 类 号：R574.62[医药卫生—消化系统]