远志总皂苷对AD模型大鼠海马nAChRα4及PSD-95表达的影响

目的:通过观察中药远志总皂苷（Tenuigenin，TEN）对阿尔茨海默病(Alzheimer’s disease，AD)模型大鼠烟碱型乙酰胆碱受体α4亚基（Nicotinic Acetylcholine Receptor subunit alpha-4，nAChRα4）和突触后致密蛋白95 (postsynaptic density 95，PSD-95)表达的影响，旨在探讨TEN对AD干预作用的机制。方法：32只雄性Wistar大鼠随机分为对照组，模型组，TEN 12.5，37.5 mg·mL^-1剂量组，应用D-半乳糖致衰老的基础上定向Meynert基底核损毁建立AD大鼠模型，TEN12.5，37.5 mg·mL^-1治疗组则在造模的同时用远志总皂苷灌胃(ig)治疗，采用免疫组化方法来检测大鼠海马CA1区nAChRα4及PSD-95的表达。结果: 模型组大鼠海马CA1区nAChRα4及PSD-95平均灰度值显著高于对照组，平均光密度值显著降低(P<0.01)；TEN 12.5，37.5 mg·mL^-1剂量组大鼠海马nAChRα4及PSD-95平均灰度值显著低于模型组，两组平均光密度值均显著增高(P<0.05)；且TEN 37.5 mg·mL^-1剂量组的平均灰度值比TEN 12.5 mg·mL^-1剂量组显著降低，平均光密度值显著增高(P<0.01)。结论：TEN可显著提高AD模型大鼠海马CA1区nAChRα4及PSD-95的表达，并具有剂量依赖性，这可能是其改善认知功能的部分机制。

The Effects of Tenuigenin on Expression of nAChRα4 and PSD95 in Alzheimer’s Disease Model Rats

Objective： To investigate the effects and the underlying mechanisms of Tenuigenin on Alzheimer’s disease by observing the effects of Tenuigenin(TEN) on expression of nicotinic acetylcholine receptor subunit alpha-4 (nAChRα4) and postsynaptic density 95(PSD-95) in Alzheimer’s disease model rat. Methods： 32 male Wistar rats were divided randomly into four groups: control group，model group，12.5 mg·mL^-1 dose TEN group and 37.5 mg·mL^-1 dose TEN group. The rat model with Alzheimer’s disease was made by injecting ibotenic acid into Meynert basal nuclei of aging rat induced by D-gal.The expressions of nAChRα4 and PSD-95 in the hippocampus CA1 were measured by immunohistochemistry method. Results： Compared with the control group，the average gray-scale values of hippocampus CA1 nAChRα4 and PSD-95 in the model group were increased significantly and the average optical density was decreased obviously (P<0.01). Compared with the model group，the average gray-scale values in the hippocampus CA1 of 37.5 mg·mL^-1 dose TEN group and 12.5 mg·mL^-1 dose TEN group were obviously decreased and the average optical density was increased significantly (P<0.05). Meanwhile，the average gray-scale value within the hippocampus CA1 of 37.5 mg·mL^-1 dose TEN group was significantly less than that in 12.5 mg·mL^-1 dose TEN group，but more distinct than that on the average optical density aspect (P<0.01). Conclusion： TEN can dose-dependently increase the expression of CA1 area nAChRα4 and PSD-95 in Alzheimer’s disease model rats，which may partly explain the beneficial effects of TEN oncognitive function.