远志总皂苷对阿尔茨海默病大鼠突触可塑性的影响
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摘要
目的：
1观察远志总皂苷对AD大鼠在体海马CA_1区神经电生理指标长时程增强的影响。
2观察远志总皂苷对AD大鼠海马CA_1区N-甲基-D-天冬氨酸受体2A亚基表达的影响。方法：
雄性Wistar大鼠随机分为对照组、模型组、高剂量远志总皂苷治疗组(37.5 mg/mL)和低剂量远志总皂苷治疗组(12.5 mg/mL)，每组8只，造模方法为腹腔注射D-半乳糖引起大鼠早衰，再用鹅膏蕈氨酸损毁Meynert核诱导大鼠发生AD的病理变化，测定并比较各组大鼠神经电生理高频刺激（HFS）前后在体海马CA_1区场兴奋性突触后电位（fEPSP）幅度的变化；测定海马CA_1免疫组织化学NR2AIOD值间接测定其表达。
结果：
1、远志总皂苷对AD大鼠在体海马CA_1区神经电生理指标长时程增强的影响：对照组fEPSP的幅度值在HFS 1分钟、30分钟和60分钟分别达到基线水平的203.17±7.47%、178.15±8.11%和164.17±7.03%水平，而模型组fEPSP幅度较对照组显著降低（p<0.05），仅分别达到基线水平的173.63±10.81%、127.12±7.38%和102.88±2.36%。低剂量远志总皂苷组fEPSP的幅度百分比值较模型组升高（p<0.05），分别达到基线水平的177.67±14.04%、131.83±4.96%和121.17±4.79%，高剂量远志总皂苷组fEPSP的幅度百分比值较模型组显著升高（p<0.05），分别达到基线水平的192.00±2.45%、168.00±2.45%和141.75±9.25%，且高剂量远志总皂苷组fEPSP的幅度百分比值较低剂量组升高（p<0.05）。
2、远志总皂苷对AD大鼠海马CA_1区突触结构N-甲基-D-天冬氨酸受体2A亚基表达的影响：对照组、AD组、低、高剂量组的NR2A积分光密度值(IOD值)分别为30.12±3.45、11.74±1.69、20.78±2.66、25.86±2.98。与对照组比较，AD模型组IOD值明显降低（p<0.05），间接反映了其表达水平降低。与模型组比较，远志总皂苷高、低剂量组的IOD值增高，间接反映其表达水平明显增高（p<0.05, p<0.05），并且高剂量组NR2A的表达较低剂量组显著（p<0.05）。
结论:
1、远志总皂苷对AD大鼠海马CA_1区神经电生理指标LTP具有易化作用。
2、远志总皂苷可上调AD大鼠海马CA_1区突触结构N-甲基-D-天冬氨酸受体2A亚基表达。
3、远志总皂苷对上述两作用呈现剂量依赖性。
0bjective①To observe the effects of Saponins in Polygala on the vivo hippocampallong-term potentiation of Alzheimer’s disease(AD) model rats, and to prove whether the effectswere dose-dependent.②To observe the effects of Saponins in Polygala on the hippocampalexpression level of NR2A in AD model rats.Methods 32 healthy male Wistar rats were randomly divided into four groups: control group,AD model group, low dose Saponins of Polygala group(12.5 mg/mL)，high dose Saponins ofPolygala group(37.5 mg/mL). AD model rats were made by injecting ibotenic acid(IBO) intothe basal forebrain Meynert nuoleus of aged rats induced by D-gal. Using Electrophysiologicaltechnique LTP was determined by comparing the average field exciatatory postsynapticpotentia(fEPSP) amplitude after high frequency stimulation(HFS) with that of baseline period.The expression level of NR2A in the hippocampal CA_1region was measured byImmunohistochemical technique.
Results：
1. The effects of Saponins in Polygala on the vivo hippocampal long-term potentiation ofAlzheimer’s disease(AD) model rats：After the HFS 1 minute, 30 minutes, and 60 minutes,thefEPSP amplitude of the control group respectively reached 203.17±7.47%, 178.15±8.11% and164.17±7.03%, while the model group fEPSP amplitude was significantly lower than the controlgroup( p<0.05), only respectively reached 173.63±10.81%, 127.12±7.38% and 102.88±2.36%.The fEPSP amplitude of high dose Saponins in polygalae group respectively reached192.00±2.45%, 168.00±2.45% and 141.75±9.25%, which were higher (p<0.05) than the lowdose group’s 177.67±14.04%, 131.83±4.96% and 121.17±4.79%. Compared with the modelgroup both of high and low dose group’s fEPSP amplitude were obviously improved (p<0.05).
2. The effects of Saponins in Polygala on the hippocampal expression level of NR2A in ADmodel rats: The integral optical density values of control group, AD model group, low dosegroup and high dose group were respectly 30.12±3.45、11.74±1.69、20.78±2.66、25.86±2.98 .Compared with control group，the pyramidal cell layers in CA_1of AD models becameindiscriminate, sparse and the expression of NR2A in the AD modle group was obivously less(p<0.05). Compared with model group, the expression of NR2A was significantly more in bothhigh dose group and low dose group(p<0.05, p<0.05). Furthermore, the expression of NR2A wassignificantly more in high dose group than low dose group (p<0.05).Conclusion: Saponins in polygala can significantly reduce the restraint to LTP induced byibotenic acid, and increase the expression of NR2A in the CA_1region of AD model rats, and improve the synaptic plasticity dose-dependently.
1观察远志总皂苷对AD大鼠在体海马CA_1区神经电生理指标长时程增强的影响。
2观察远志总皂苷对AD大鼠海马CA_1区N-甲基-D-天冬氨酸受体2A亚基表达的影响。方法：
雄性Wistar大鼠随机分为对照组、模型组、高剂量远志总皂苷治疗组(37.5 mg/mL)和低剂量远志总皂苷治疗组(12.5 mg/mL)，每组8只，造模方法为腹腔注射D-半乳糖引起大鼠早衰，再用鹅膏蕈氨酸损毁Meynert核诱导大鼠发生AD的病理变化，测定并比较各组大鼠神经电生理高频刺激（HFS）前后在体海马CA_1区场兴奋性突触后电位（fEPSP）幅度的变化；测定海马CA_1免疫组织化学NR2AIOD值间接测定其表达。
结果：
1、远志总皂苷对AD大鼠在体海马CA_1区神经电生理指标长时程增强的影响：对照组fEPSP的幅度值在HFS 1分钟、30分钟和60分钟分别达到基线水平的203.17±7.47%、178.15±8.11%和164.17±7.03%水平，而模型组fEPSP幅度较对照组显著降低（p<0.05），仅分别达到基线水平的173.63±10.81%、127.12±7.38%和102.88±2.36%。低剂量远志总皂苷组fEPSP的幅度百分比值较模型组升高（p<0.05），分别达到基线水平的177.67±14.04%、131.83±4.96%和121.17±4.79%，高剂量远志总皂苷组fEPSP的幅度百分比值较模型组显著升高（p<0.05），分别达到基线水平的192.00±2.45%、168.00±2.45%和141.75±9.25%，且高剂量远志总皂苷组fEPSP的幅度百分比值较低剂量组升高（p<0.05）。
2、远志总皂苷对AD大鼠海马CA_1区突触结构N-甲基-D-天冬氨酸受体2A亚基表达的影响：对照组、AD组、低、高剂量组的NR2A积分光密度值(IOD值)分别为30.12±3.45、11.74±1.69、20.78±2.66、25.86±2.98。与对照组比较，AD模型组IOD值明显降低（p<0.05），间接反映了其表达水平降低。与模型组比较，远志总皂苷高、低剂量组的IOD值增高，间接反映其表达水平明显增高（p<0.05, p<0.05），并且高剂量组NR2A的表达较低剂量组显著（p<0.05）。
结论:
1、远志总皂苷对AD大鼠海马CA_1区神经电生理指标LTP具有易化作用。
2、远志总皂苷可上调AD大鼠海马CA_1区突触结构N-甲基-D-天冬氨酸受体2A亚基表达。
3、远志总皂苷对上述两作用呈现剂量依赖性。
0bjective①To observe the effects of Saponins in Polygala on the vivo hippocampallong-term potentiation of Alzheimer’s disease(AD) model rats, and to prove whether the effectswere dose-dependent.②To observe the effects of Saponins in Polygala on the hippocampalexpression level of NR2A in AD model rats.Methods 32 healthy male Wistar rats were randomly divided into four groups: control group,AD model group, low dose Saponins of Polygala group(12.5 mg/mL)，high dose Saponins ofPolygala group(37.5 mg/mL). AD model rats were made by injecting ibotenic acid(IBO) intothe basal forebrain Meynert nuoleus of aged rats induced by D-gal. Using Electrophysiologicaltechnique LTP was determined by comparing the average field exciatatory postsynapticpotentia(fEPSP) amplitude after high frequency stimulation(HFS) with that of baseline period.The expression level of NR2A in the hippocampal CA_1region was measured byImmunohistochemical technique.
Results：
1. The effects of Saponins in Polygala on the vivo hippocampal long-term potentiation ofAlzheimer’s disease(AD) model rats：After the HFS 1 minute, 30 minutes, and 60 minutes,thefEPSP amplitude of the control group respectively reached 203.17±7.47%, 178.15±8.11% and164.17±7.03%, while the model group fEPSP amplitude was significantly lower than the controlgroup( p<0.05), only respectively reached 173.63±10.81%, 127.12±7.38% and 102.88±2.36%.The fEPSP amplitude of high dose Saponins in polygalae group respectively reached192.00±2.45%, 168.00±2.45% and 141.75±9.25%, which were higher (p<0.05) than the lowdose group’s 177.67±14.04%, 131.83±4.96% and 121.17±4.79%. Compared with the modelgroup both of high and low dose group’s fEPSP amplitude were obviously improved (p<0.05).
2. The effects of Saponins in Polygala on the hippocampal expression level of NR2A in ADmodel rats: The integral optical density values of control group, AD model group, low dosegroup and high dose group were respectly 30.12±3.45、11.74±1.69、20.78±2.66、25.86±2.98 .Compared with control group，the pyramidal cell layers in CA_1of AD models becameindiscriminate, sparse and the expression of NR2A in the AD modle group was obivously less(p<0.05). Compared with model group, the expression of NR2A was significantly more in bothhigh dose group and low dose group(p<0.05, p<0.05). Furthermore, the expression of NR2A wassignificantly more in high dose group than low dose group (p<0.05).Conclusion: Saponins in polygala can significantly reduce the restraint to LTP induced byibotenic acid, and increase the expression of NR2A in the CA_1region of AD model rats, and improve the synaptic plasticity dose-dependently.
引文
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