延胡索和L-THP对吗啡依赖大鼠胃肠多巴胺系统的影响  

Effect of Corydalis yanhusuo and L-THP on Gastrointestinal Dopamine System in Morphine-Dependent Rats

作　　者：徐靖宇[1,2] 白威峰[3] 丘成楷 涂平[3] 余守洋[3] 罗素元[3] 

机构地区：[1]遵义医学院附属医院消化内科,贵州遵义563099 [2]遵义医学院生理学教研室,贵州遵义563099 [3]遵义医学院细胞生物学教研室,贵州遵义563099

出　　处：《中药材》2015年第12期2568-2572,共5页Journal of Chinese Medicinal Materials

基　　金：国家自然科学基金(30860373)

摘　　要：目的:研究延胡索及左旋延胡索乙素(L-THP)对吗啡依赖大鼠胃肠损伤的保护作用及其机制。方法:雄性SD大鼠180只随机分为9组,20只/组,分别为正常对照组、模型组、生理盐水治疗组及延胡索低、中、高剂量组和L-THP低、中、高剂量组。除正常对照组外各组大鼠颈背部皮下吗啡剂量递增注射后,分别置于黑箱和白箱中进行条件性位置偏爱(CPP)训练,连续10 d(白箱为吗啡伴药箱),在最后一次训练48 h后进行条件性位置偏爱实验测试,并处死正常对照组及模型组大鼠检测各项指标,以确认成功建立吗啡条件性位置偏爱模型。造模成功当日,延胡索低、中、高剂量组分别按生药0.5、1、2 g/kg灌胃延胡索水提液,L-THP低、中、高剂量组分别灌胃L-THP0.94、1.88、3.76 mg/kg,生理盐水治疗组灌胃生理盐水,治疗6 d后再次条件性位置偏爱测试后处死取材。多巴胺递质含量和D2R的表达检测分别采用荧光分光光度法和Western blot技术。结果:与生理盐水治疗组比较,延胡索1、2 g/kg组及L-THP 1.88、3.76 mg/kg组大鼠在白箱停留时间显著减少(P<0.01),同时其胃和十二指肠多巴胺递质含量升高(P<0.01);胃贲门、胃体和十二指肠中D2R表达显著下调(P<0.01)。结论:延胡索和L-THP能逆转吗啡依赖胃肠损伤大鼠胃和十二指肠多巴胺递质的异常减少和D2R的异常增加,这可能是其保护吗啡依赖继发胃肠损伤的作用机制之一。Objective： To investigate the protective mechanism of Corydalis yanhuso and L-THP in morphine-dependent gastrointestinal injury rats. Methods： 180 male rats were randomly divided into nine groups,20 rats for each group： saline group（ N）,model group（ M）,NS treatment group and three different dosage of Corydalis yanhusuo and L-THP groups（ low dose group,middle dose group and high dose group）. The rat CPP（ conditioned place preference） model was established by injecting the rats with an increasing dosage of morphine,all groups received CPP training in a black compartments and white ones（ drug-paired compartment） for ten days. At 48 h after the final training,the performance of CPP models were assessed to make sure all models were exported correctly. Then the treatment groups were administered with different concentration of Corydalis yanhuso（ 0. 5,1 and 2 g / kg） and L-THP（ 0. 94,1. 88 and 3. 76 mg /kg） for six days. All rats were immediately killed after finish the last CPP test. For each group,ten rats were killed to detect the contents of DA in the stomach and duodenum through the fluorescence spectrophotometer. The expression levels of D2receptor（ D2R） in different tissues（ gastric cardia,gastric body,pylorus and duodenum） were checked by Western-blot in the other rats. Results： In the NS treatment group,the time when rats stay in the white ones were significantly decreased compared with the Corydalis yanhusuo treated groups（ 1 and 2 g/kg） and L-THP treated groups（ 1. 88 and 3. 76 mg/kg）（ P〈0. 01）,the high expression of DA contents in the stomach and duodenum were significantly decreased（ P〈0. 01）. However the protein level of D2 R were notably lower in gastric cardia,gastric body,pylorus and duodenum（ P〈0. 01）. Conclusion： Injuries of the gastrointestinal tract followed lower DA contents and an abnormal increase of D2 R in the stomach and duodenum of rats,which induced by morphine-dependent could be reversed by treatment with Corydalis yanh

关 键 词：延胡索 L-THP 吗啡依赖 消化系统 多巴胺 多巴胺D2受体 

分 类 号：R285.5[医药卫生—中药学]