培元解郁方对糖皮质激素诱导大鼠抑郁模型TRP-KYN代谢的影响及神经元可塑性调节机制  

Effects of Peiyuan Jieyu Formula on TRP-KYN metabolic pathway and its neuron protection mechanism in depressed rats induced by glucocorticoid

作　　者：李海娜[1] 李丽娜 王淑艳 范盎然 于雪 王萍萍[1] 刘保秀 畅洪昇[1] 

机构地区：[1]北京中医药大学中药学院,北京100102 [2]北京中医药大学中医学院

出　　处：《北京中医药大学学报》2017年第12期1011-1017,共7页Journal of Beijing University of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(No.81373584)~~

摘　　要：目的研究培元解郁方对糖皮质激素诱导大鼠抑郁模型的抗抑郁作用,对色氨酸-犬尿氨酸(TRP-KYN)代谢的影响以及对海马和皮层神经元可塑性的影响。方法将70只雄性大鼠随机分为7组,每组10只,分别为空白组、模型组、氟西汀组、天丝饮组、四逆散组和培元解郁方中、高剂量组,糖皮质激素注射28 d建立大鼠抑郁模型,造模结束后进行敞箱测试和糖水消耗测试;采用HPLC-MS/MS技术检测血清色氨酸(TRP)、犬尿氨酸(KYN)、犬尿烯酸(KA)、喹啉酸(Q)含量,RT-PCR检测海马和皮层神经元内N-甲基-D-天冬氨酸受体(NR)、脑源性神经营养因子(BDNF)表达水平。结果糖皮质激素注射28 d后,与空白组比较模型组大鼠糖水消耗量、敞箱活动的总得分显著降低(P<0.05),KYN/TRP、KYN/KA比值显著升高(P<0.05),海马BDNF mRNA表达显著降低(P<0.05),皮层NR mRNA表达显著升高(P<0.05)。培元解郁方可显著提高大鼠糖水消耗量(P<0.05),敞箱活动总得分(P<0.05),降低KYN/TRP、KYN/KA比值(P<0.05),升高KYN/Q比值(P<0.05),升高海马BDNF mRNA表达水平(P<0.05),降低皮层NR mRNA表达(P<0.05)。结论培元解郁方可以通过下调TRP-KYN代谢,抑制神经毒性,提高神经保护;通过促进皮层和海马尤其是皮层的神经元可塑性发挥抗抑郁作用。Objective To study the effects of Peiyuan Jieyu Formula（ PYJYF） on rats treated with glucocorticoid,its influences on metabolism of the TRP-KYN pathway and the impacts on hippocampal and cortical neuronal plasticity. Methods 70 rats were randomly divided into the following 7 groups（ n = 10 in each group） ： normal blank group,model group,fluoxetine group,mid-and high-dose Tiansi Yin（ TSY） groups,Sini San（ SNS） groups,and PYJYF groups. Rat model of depression was established by intraperitoneal injection of glucocorticoid for 28 days. Sucrose solution consumption and Open-field test were conducted. The content of TRP,KYN,KA and Q in serum was measuredby using HPLC-MS/MS technique. The mRNA expressions of NR and BDNF in brain tissue were measured by using RT-PCR.Results 28 days after the injection of glucocorticoid in model group,the consumption of sucrose solution and total score in open-field test was significantly decreased（ P〈0. 05）. The ratios of KYN/TRP and KYN/KA increased significantly（ P〈0. 05）. The mRNA expression level of BDNF in hippocampal decreased significantly（ P〈0. 05）. The mRNA expression level of NR increased significantly（ P〈0. 05）.Peiyuan Jieyu Formula increased the consumption of sucrose solution（ P〈0. 05）,the total score in openfield test,the ratios of KYN/Q and the mRNA expression level of BDNF in hippocampus（ P〈0. 05） when compared with the model group. The ratios of KYN/TRP and KYN/KA（ P〈0. 05） and the mRNA expression level of NR in cortex（ P〈0. 05） of Peiyuan Jieyu Formula group decreased. Conclusion Peiyuan Jieyu Formula can reduce the metabolism of TRP-KYN,inhibit neurotoxicity,improve neural protection,and promote the hippocampal and cortical neural plasticity.

关 键 词：糖皮质激素 TRP-KYN代谢 海马 皮层 神经可塑性 大鼠 

分 类 号：R285.5[医药卫生—中药学]