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培元解郁方对急性糖皮质激素诱导SD大鼠的抗抑郁作用及TRY-KYN代谢途径的调节 预览

Antidepressant Effect of Peiyuan Jieyu Decoction and Its Regulation on TRY-KYN Metabolic Pathway on Acute glucocorticoid on SD rats
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摘要 目的:研究培元解郁方的抗抑郁作用以及对色氨酸(TRY)-犬尿氨酸(KYN)代谢的调节机制。方法:建立氢化可的松大鼠抑郁模型,以蔗糖消耗反映大鼠的抑郁状态,采用高效液相-质谱联用(HPLC-MS/MS)技术检测脑组织KYN、TRY、喹啉酸(QUIN)、犬尿烯酸(KA)含量,实时荧光定量PCR技术测定肝组织中色氨酸2,3-双加氧酶(TDO)mRNA表达水平和脑组织海马中吲哚胺2,3-双加氧酶(IDO)、5-HT1A的mRNA表达。结果:造模21 d后,大鼠对蔗糖的偏好降低,KYN/TRY比值升高,QUIN含量升高,KA含量降低,TDO mRNA的表达水平增加,5-HT1AmRNA的表达水平降低,差异有统计学意义(P〈0.05)。各给药组能提高大鼠对蔗糖的偏好,差异有统计学意义(P〈0.05)。各给药组均能显著降低KYN/TRY比值,差异有统计学意义(P〈0.05),培元解郁方中剂量组和天丝饮组能显著提高KA的含量,降低QUIN的含量,差异有统计学意义(P〈0.05)。天丝饮能明显降低肝脏中TDO和海马中IDO mRNA的表达,差异有统计学意义(P〈0.05)。四逆散和培元解郁方中、高剂量能够增加海马中5-HT1AmRNA的表达,差异有统计学意义(P〈0.05)。结论:天丝饮、四逆散和培元解郁方均有抗抑郁药样作用,机制与降低TRY-KYN代谢的关键酶mRNA表达,降低神经毒性代谢产物和增加神经保护性代谢产物,从而提高神经元保护作用,以及增加5-HT1A的mRNA表达有关。 Objective: To study the antidepressant effects of Peiyuan Jieyu Decoction and the regulatory mechanism of the tryptophan-kynurenine( TRY-KYN) metabolic pathway. Methods: The rat model of depression induced by intraperitoneal injection hydrocortisone was built. The symptoms of depression were observed by sucrose preference experiment. The contents of tryptophane,kynurenine,kynurenic acid and quinaldinic acid in brain tissue were detected by HPLC-MS/MS technique. The mRNA expression levels of TDO in liver tissue,IDO and 5-HT1 Ain brain tissue were detected by using real-time PCR. Results: After 21 days' acute stress,the preference in sucrose was reduced. The ratio of KYN/TRY and the content of QUIN were increased. The content of KA was decreased. The expression of TDO mRNA increased and the expression of 5-HT1 AmRNA decreased( P 〈0. 05). The Fluoxetine group,Tiansi decoction group,Sini decoction group,high dose and middle dose of Peiyuan Jieyu decoction group could improve the preference in sucrose preference experiment( P 〈0. 05). Each treatment group could obviously reduce the ratio of KYN/TRY( P 〈0. 05). Tiansi decoction and middle dose of Peiyuan Jieyu decoction could significantly improve the content of KA,and decrease the content of QUIN P 〈0. 05). Tiansi decoction could obviously decrease the expression of TDO mRNA in liver and the expression of IDO mRNA in hippocampus( P 〈0. 05). Sini decoction,middle dose and high dose of Peiyuan Jieyu decoction could increase the expression of 5-HT1 AmRNA in hippocampus( P 〈0. 05). Conclusion: Traditional Chinese medicine groups have antidepressant effects. Its mechanism may be connected with reducing the expression of the key enzyme mRNA in TRY-KYN metabolic pathway,improving the neuron protective effect by reducing neurotoxic metabolites and increasing neuroprotective metabolites,and increasing the expression of 5-HT1 A.
作者 杨桃 张静 李丽娜 鲁艺 王淑艳 黄翔 张波 畅洪昇 Yang Tao1 , Zhang Jing1 , Li Lina2 , Lu Yi2 , Wang Shuyan2 , Huang Xiang2 , Zhang Bo1 , Chang Hongsheng1 ( 1. School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China; 2. School of Preelinical Medicine, Beijing University of Chinese Medicine, Beijing 100029, China)
出处 《世界中医药》 CAS 2018年第8期1964-1967,1971共5页
基金 国家自然科学基金项目(81373584)
关键词 培元解郁方 抗抑郁 色氨酸-犬尿氨酸代谢途径 Peiyuan Jieyu Decoction Antidepression TRY-KYN
作者简介 杨桃(1988.12-),女,硕士研究生在读,研究方向:中药药效及作用机制研究,E-mail:Yangtao10411@sina.cn;通信作者:畅洪昇(1971.10-),男,博士,副教授,硕士研究生导师,研究方向:中药药效及作用机制研究,E-mml:chs1971@sina.com
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