苦马豆素对家兔脑组织NO-cGMP-Glu途径的影响

Effects of swainsonine on NO-cGMP-Glu pathway of brain tissue in rabbits

探讨苦马豆素对家兔脑组织一氧化氮(NO)、环磷鸟苷(cGMP)和游离谷氨酸(Glu)的影响,进一步揭示苦马豆素的毒性作用机理。将24只家兔随机分为4组,即对照组和试验Ⅰ、Ⅱ、Ⅲ组。将小花棘豆全草粉碎后,按Ⅰ组添加15%(含苦马豆素30mg/kg)、Ⅱ组添加30%(含苦马豆素60mg/kg)、Ⅲ组添加45%(含苦马豆素90mg/kg)的比例制作混合饲料,饲喂至典型临床症状出现为止。攻毒后14、35、70d每次每组随机采集2只家兔的全脑,检测家兔不同脑区NO、cGMP和Glu含量的变化。结果显示,从35d起,试验Ⅰ组家兔大脑、小脑、丘脑及海马的NO、cGMP及Glu含量均显著高于对照组(P<0.05);试验Ⅱ、Ⅲ组家兔大脑、小脑、丘脑及海马的NO、cGMP及Glu含量均极显著高于对照组(P<0.01),但3个试验组脑干中3种物质含量与对照差异均不显著(P>0.05)。同一试验组中小脑3种物质的含量变化较海马、大脑和丘脑明显。结果表明,不同浓度苦马豆素对家兔脑组织NO、cGMP及Glu含量有显著影响,且具有一定的时间-剂量效应关系,小脑、海马、大脑和丘脑是苦马豆素作用的靶区,通过影响这几个脑区信号转导而产生毒性作用。

Twenty four rabbits were divided into 4groups(the control group and experimental groupⅠ,Ⅱ,Ⅲ)to investigate the effects of swainsonine on the content of nitric oxide(NO),cGMP and glutamate(Glu)in brain tissue,and reveal the toxicity mechanism of swainsonine in future.The dried plant of Oxytropis glabra DC was comminnuted,and different amounts of the grass powder(added 15%,30%and 45% is corresponding to swainsonine content of 30 mg/kg,60mg/kg,90 mg/kg)were mixed with the feeds in the three experimental group.The rabbits consumed the forages freely until typical symptoms were observed.Two rabbits were selected randomly from each group on the 14 th,35th and 70 th day respectively,the brain was collected and the contents of NO,cGMP and Glu in different encephalic regions were measured.The results demonstrated that the contents of NO,cGMP and Glu in cerebrum,cerebellum,thalamus and hippocampus in experimental groupⅠ were significantly higher than normal control group from 35 th day(P<0.05),the contents of NO,cGMP and Glu in cerebrum,cerebellum,thalamus and hippocampus in experimental groupⅡ,Ⅲ were very significantly higher than normal control group(P<0.01),but the difference of contents of NO,cGMP and Glu were not obviou in brainstem(P>0.05).The change of contents of NO,cGMP and Glu in cerebellum were obviously higher than cerebrum thalamus and hippocampus.The results showed that swainsonine has remarkable effects on the contents of NO,cGMP and Glu of brain in rabbits,furthermore a time-effect as well as a dose-effect relationship was observed,indicating that four regions were the effective target sites of swainsonine in the brain tissue,we concluded that swainsonine could produce poisoning effect by promoting cerebrum,cerebellum,thalamus and hippocampus releasing NO,cGMP and Glu.