芍药苷对血虚肝郁证模型大鼠海马谷氨酸及其不同类型受体mRNA表达的影响

Effects of paeoniflorin on expression of Glu and different glutamate receptors in hippocampus of rats with syndrome of stagnation of liver qi and blood deficiency

目的:研究血虚肝郁证大鼠海马谷氨酸(Glu)及不同类型受体NR1、NR2A、NR2B、GluR1、mGluR5 mRNA的表达及芍药苷的干预作用。方法:正常组、模型组、20mg/kg芍药苷组、40mg/kg芍药苷组,造模第1天开始给药,正常组给等量超纯水,其余各组灌胃予以相应浓度药物,共造模21d。治疗结束后,取脑组织,剥离海马,采用邻苯二甲醛(OPA)柱前衍生HPLC荧光检测法测定Glu含量,采用实时荧光定量聚合酶链反应法(RTqPCR)检测NR1、NR2A、NR2B、GluR1、mGluR5等5种受体亚单位mRNA的表达。结果:血虚肝郁证候模型大鼠海马组织中Glu含量显著升高(P<0.05),且不同Glu受体亚基表达不同,其中NR2A和GluR1 mRNA的表达显著升高(P<0.01),NR1、NR2B mRNA表达有升高的趋势,而mGluR5表达无明显变化,给予芍药苷可使海马组织中Glu含量显著降低(P<0.05),可下调NR2A、GluR1、mGluR5 mRNA表达(P<0.01,P<0.05)。结论:血虚肝郁证模型大鼠脑内存在Glu能神经调节异常,白芍的养血柔肝作用,能够通过调节NO/cGMP信号通路上个的多个靶点发挥效果。

Objective： To observe the mRNA expression of glutamate（Glu） and different glutamate receptors as NR1, NR2A, NR2B, GluR1 and m GluR5 in the hippocampus of rats with syndrome of stagnation of liver qi and blood deficiency and the intervention effect of paeoniflorin. Methods： The rats were divided into normal group, model group, 20mg/kg paeoniflorin group and 40mg/kg paeoniflorin group. Since the 1st day of modeling, the rats in normal group received gavage administration with the same amount of pure water, while rats in the other groups received gavage administration with corresponding drugs. The modeling process lasted for 21 days. After treating, the hippocampus tissue was obtained, and the Gluconcentration in hippocampus tissue was determined by using HPLC method. The mRNA expression of NR1, NR2A, NR2B, GluR1 and m GluR5 was tested by using RT-q PCR. Results： The content of Gluin hippocampus tissue of rats in model group increased significantly compared with normal group（P〈0.05）. The mRNA expression of different glutamate receptors was various, such as the mRNA expressions of NR2A and GluR1 increased significantly（P〈0.01）, the mRNA expressions of NR1 and NR2B showed a trend of increasing, and the mRNA expressions of m GluR5 had no significant change. Paeoniflorin could reduce the content of Gluand the mRNA expressions of glutamate receptors as NR2A, GluR1 and m GluR5 in hippocampus tissue of model rats（P〈0.01, P〈0.05）. Conclusion： The regulatory function of glutamate nerve in brain of rats with syndrome of stagnation of liver qi and blood deficiency is abnormal, Debark peony root can nourishing blood and softening liver, this effect can play efficiency by regulating the multiple targets of NO/cGMP pathway.