正天丸对大鼠海马内嗅区前穿质-齿状回通路及谢弗侧枝-CA1通路的突触传递作用研究

目的：为了研究正天丸对大鼠海马内嗅区前穿质-齿状回通路及谢弗侧枝-CA1通路的突触传递作用。方法：将SD大鼠随机分为五组：空白组，阳性对照组，偏头痛模型组，正天丸低剂量组及正天丸高剂量组。以皮下注射三硝酸甘油酯 (10 mg/kg) 的大鼠为偏头痛模型，氟桂嗪 (0.9 mg/kg) 为阳性对照药，我们采取电生理实验技术，研究正天丸对麻醉大鼠海马内嗅区前穿质-齿状回通路以及正天丸对大鼠离体海马脑片谢弗侧枝-CA1通路的突触传递作用的影响。结果：与对照组相比，正天丸 (1.08 g/kg) 对麻醉大鼠海马内嗅区前穿质-齿状回通路内高频刺激诱导的LTP指标，PS幅度有显著的增强作用；而三硝酸甘油酯 (10 mg/kg) 可以显著的降低PS的幅度；正天丸 (0.54 g/kg) 和氟桂嗪 (0.9 mg/kg)均对PS幅度没有增强作用。与模型组相比，正天丸 (1.08 g/kg)，正天丸 (0.54 g/kg) 和氟桂嗪 (0.9 mg/kg) 均对PS幅度有显著的增强作用。在离体海马脑片实验中，与对照组相比，正天丸 (1.08 g/kg) 对离体海马脑片谢弗侧枝-CA1通路内高频刺激诱导的LTP指标，fEPSP斜率有显著的增强作用；而三硝酸甘油酯 (10 mg/kg) 可以显著的降低fEPSP斜率；正天丸 (0.54 g/kg) 和氟桂嗪 (0.9 mg/kg) 均对fEPSP斜率没有显著的增强作用。与模型组相比，正天丸 (1.08 g/kg)、正天丸 (0.54 g/kg) 和氟桂嗪 (0.9 mg/kg) 均对fEPSP斜率有显著的增强作用。结论：结合我们之前的研究，可以得出正天丸对TRPV1蛋白和海马LTP的作用可能是正天丸作为治疗偏头痛药物的重要分子机制。

Zhengtian Pills accelerated long term potentiation both in schaffer collateral -CA1 and perforant path-dentate gyrus synapses

Objective

To investigate the effects of Zhengtian Pills (ZTP) on long term potentiation (LTP) both in Schaffer-CA1 in vitro and perforant path-dentate gyrus (PP-DG) synapses in vivo.

Methods

Sprague-Dawley rats were randomly divided into five groups: control, positive control, migraine model, low-, and high-dose ZTP groups. Glyceryl trinitrate (10?mg/kg) was injected subcutaneously to make migraine rat model. Flunarizine (0.9?mg/kg) was set as positive control. Extracellular recording technique in vivo was used to record the effects of ZTP on LTP of PP-DG pathway in anesthetized rats; Using extracellular recording technique in vitro, the effects of ZTP on LTP of Schaffer Collateral-CA1 pathway in rat hippocampal slices were investigated.

Results

Compared to the control group, ZTP (1.08?g/kg) significantly enhanced population spike amplitude in PP-DG pathway; Glyceryl trinitrate (10?mg/kg) significantly reduced population spike amplitude in PP-DG pathway; Neither ZTP (0.54?g/kg) nor Flunarizine (0.9?mg/kg) had significant effects on LTP in PP-DG pathway. Compared to the model group, ZTP (1.08?g/kg), ZTP (0.54?g/kg), and flunarizine (0.9?mg/kg) significantly enhanced population spike amplitude in PP-DG pathway. Compared to the control group, ZTP (1.08?g/kg) significantly enhanced field excitatory postsynaptic potential (fEPSP) slope in Schaffer Collateral-CA1 pathway; Glyceryl trinitrate (10?mg/kg) significantly reduced fEPSP slope in Schaffer Collateral-CA1 pathway; Neither ZTP (0.54?g/kg) nor flunarizine (0.9?mg/kg) significant effects on LTP in Schaffer Collateral-CA1 pathway, Compared to the model group, ZTP (1.08?g/kg), ZTP (0.54?g/kg), and Flunarizine (0.9?mg/kg) had significantly enhanced fEPSP slope in Schaffer Collateral-CA1 pathway.

Conclusion

Combined with the previous study, the results gave a clue that the effects of ZTP on TRPV1 and hippocampal LTP or their interactions could be the important molecular mechanisms of ZTP acting as migraine and headache medication.