基于代谢组学的四逆散干预创伤后应激障碍大鼠模型的作用研究
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摘要
目的研究四逆散干预创伤后应激障碍(PTSD)大鼠的分子生物学机制。方法按照体重将SD大鼠随机分为5组:空白对照组、模型组、阴性对照组、阳性对照组和实验组,每组10只。除空白对照组外,其他4组动物均复制模型。空白对照组与模型组均不接受药物干预,阴性对照组灌胃等体积0. 9%Na Cl,阳性对照组灌胃盐酸帕罗西汀溶液0. 42 mg·mL~(-1),实验组灌胃四逆散水煎液(含生药0. 24 g·mL~(-1));于应激造模前1 h,每次灌胃给药10 mL·kg~(-1),1次/天,共计7 d。于末次给药5 h后,统一采集血清。用代谢组学方法筛选大鼠血清特征性分子。结果模型组与空白对照组比较,存在差异代谢产物15个,含量均升高;阴性对照组与模型组比较,无明显差异离子;实验组与阴性对照组比较,存在差异代谢物11个,其中组氨酸和5-羟基阿魏酸甲酯的含量增高,其余分子含量降低;阳性对照组存在差异代谢物共1个,即anopterine,含量降低。结论 PTSD大鼠血清差异代谢分子存在不同程度的上调或下调,这些代谢分子的异常表达可能是PTSD的重要神经内分泌机制。
Objective To study the function mechanism of the Sinisan on serum molecular expression in rats with post-traumatic stress disorder( PTSD). Methods Sprague Dawley( SD) rats were divided equally into five groups: blank control group,model group,negative control group,positive control group and experimental group. The blank control group did not copy the model,do not receive treatment,the normal feeding.Model group,repetitive PTSD model was induced by current stimulation,but not treated. Negative control group,equal volume of 0. 9% Na Cl.Positive control group( paroxetine hydrochloride 0. 42 mg·mL~(-1)) and experimental group( Sinisan,containing crude drug 0. 24 mg·mL~(-1)). It received drug( 10 mL·kg~(-1)) 1 h before the mode establishment. Once a day,for a total of 7 d. At the end of the last administration for 5 h,the serum samples were collected uniformly in each group. Screening of characteristic molecules in rat serum by metabolic method. Results Compared with blank control group,there were fifteen materials were identified by database, and concentration increased. Compared with model group,there was no significant difference in the negative control group. Compared with negative control group,there were significantdifferences between the two drug groups. There were eleven differential metabolites in the experimental group,the concentration of histidine and 5-hydroxy methyl ferulic acid increased. There was one different metabolites in the positive control group,and only one of them was identified by the database,that was,anopterine,the concentration decreased.Conclusion The differential metabolic molecules in serum of PTSD rats are up-regulated or down-regulated to varying degrees. The abnormal expression of metabolites may be an important neuroendocrine mechanism of PTSD.
Objective To study the function mechanism of the Sinisan on serum molecular expression in rats with post-traumatic stress disorder( PTSD). Methods Sprague Dawley( SD) rats were divided equally into five groups: blank control group,model group,negative control group,positive control group and experimental group. The blank control group did not copy the model,do not receive treatment,the normal feeding.Model group,repetitive PTSD model was induced by current stimulation,but not treated. Negative control group,equal volume of 0. 9% Na Cl.Positive control group( paroxetine hydrochloride 0. 42 mg·mL~(-1)) and experimental group( Sinisan,containing crude drug 0. 24 mg·mL~(-1)). It received drug( 10 mL·kg~(-1)) 1 h before the mode establishment. Once a day,for a total of 7 d. At the end of the last administration for 5 h,the serum samples were collected uniformly in each group. Screening of characteristic molecules in rat serum by metabolic method. Results Compared with blank control group,there were fifteen materials were identified by database, and concentration increased. Compared with model group,there was no significant difference in the negative control group. Compared with negative control group,there were significantdifferences between the two drug groups. There were eleven differential metabolites in the experimental group,the concentration of histidine and 5-hydroxy methyl ferulic acid increased. There was one different metabolites in the positive control group,and only one of them was identified by the database,that was,anopterine,the concentration decreased.Conclusion The differential metabolic molecules in serum of PTSD rats are up-regulated or down-regulated to varying degrees. The abnormal expression of metabolites may be an important neuroendocrine mechanism of PTSD.
引文
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[2]MAUJEA N,ANNIC K,GULL O,et al. Post-traumatic stress symptom clusters in acute whiplash associated disorder and their prediction of chronic pain-related disability[J]. Pain Reports,2017,2(6):1-6.
[3]巩帅.不同生理或应激状态小鼠血清中皮质醇和皮质酮的变化规律及相关性[D].山东泰安:山东农业大学,2015.
[4]施新猷.现代医学实验动物学[M].北京:人民卫生出版社,2000:334.
[5]王禾. PTSD动物模型的制备及其发病机理的研究[D].重庆:第三军医大学,2003.
[6]刘林.中药含药血浆与血清有效成分比较及血浆药理学方法研究[D].长沙:湖南中医药大学,2016.