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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 effect and mechanism of Corydalis and L-tetrahydropalmatine (L-THP) on gastrointestinal injury in morphine dependent rats. Methods: One hundred and eighty male Sprague-Dawley rats were randomly divided into 9 groups (20 rats / group), which were normal control group, model group, saline treatment group and low, medium and high dose of Corydalis group, Dose group. Except for the normal control group, rats in each group were injected subcutaneously with increasing doses of subcutaneous morphine, and then placed in black box and white box for conditioned place preference (CPP) training for 10 days (white box was morphine with medicine box) 48h after the last training conditional conditional preference test, and executed normal control group and model rats were detected indicators to confirm the successful establishment of morphine conditional positional preference model. On the day of successful modeling, the low, medium and high dose of Corydalis japonicus were treated with 0.5,1,2 g / kg crude drug of Rhizoma Corydalis, L-THP 0.94, 1.88 and 3.76 mg / kg respectively. The saline treatment group was given normal saline, and after 6 days of treatment, the conditioned place preference test was again performed. Dopamine neurotransmitter content and D2R expression were detected by fluorescence spectrophotometry and Western blot. Results: Compared with the saline group, the retention time in white box was significantly decreased (P <0.01) in the 1,2 g / kg group and the L-THP 1.88,3.76 mg / kg group (P <0.01). The expression of D2R in gastric cardia, gastric body and duodenum was significantly down-regulated (P <0.01). CONCLUSION: Corydalis and L-THP can reverse the abnormal decrease of D2 and dopamine in the stomach and duodenum of rats with morphine-dependent gastrointestinal injury, which may be the mechanism of protection of morphine-dependent secondary gastrointestinal injury one.