远志总皂苷对AD模型大鼠海马nAChRα4及PSD-95表达的影响

The Effects of Tenuigenin on Expression of nAChRα4 and PSD-95 in Alzheimer’s Disease Model Rats

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,TEN 12.5,37.5 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剂量组降低显著,平均光密度值增高显著(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。

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(PSD95)in Alzheimer’s disease model rats.Methods:32 male Wistar rats were divided randomly into four groups:control group,model group,12.5 mg.mL-1dose 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 on cognitive function.