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

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 glu-cocorticoid, 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 de-creased 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 open-field 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 ex-pression 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.