远志总皂苷对AD模型大鼠海马Ng及pCaMKⅡα表达的影响

The effects of tenuigenin on expression of neurogranin and pCaMKⅡα in Alzheimer's disease model rats

目的观察远志总皂苷(TEN)对阿尔茨海默病(AD)模型大鼠海马CA1区神经颗粒素(Ng)以及磷酸化的钙/钙调蛋白依赖性蛋白激酶Ⅱα亚基(pCaMKⅡα)表达的影响,探讨TEN防治AD的作用机制。方法将60只雄性Wistar大鼠随机分为对照组,模型组,TEN低剂量治疗组(12.5mg/ml)和TEN高剂量治疗组(37.5 mg/ml),每组15只,模型组予以腹腔注射D-半乳糖(D-gal)致衰并联合鹅膏覃氨酸(IBO)定向Meynert基底核损毁法建立AD大鼠模型,TEN低、高剂量治疗组则在造模的同时TEN灌胃治疗8w,对照组则用等体积的生理盐水代替D-gal和IBO。采用免疫组化方法来检测大鼠海马CA1区Ng及pCaMKⅡα的表达。结果模型组大鼠海马CA1区Ng及pCaMKⅡα平均吸光度值比对照组显著降低(P<0.01);TEN治疗组两组平均吸光度值均较模型组显著增高(P<0.01);且TEN高剂量治疗组(37.5 mg/ml)的平均吸光度值比TEN低剂量治疗组(12.5mg/ml)显著增高(P<0.01)。结论 TEN可显著升高AD模型大鼠海马CA1区Ng及pCaMKⅡα的表达,且具有剂量依赖性。

Objective To observe the effects of tenuigenin （ TEN） on expression of neurogranin （ Ng） and the phosphorylation of calcium/calmodulin-dependent protein kinasetype Ⅱ-alpha （ pCaMKⅡα） in Alzheimer ’ s disease model rats and its possible mechanism .Methods 60 male Wistar rats were divided randomly into four groups：control group,model group,low-dose TEN treatment group（12.5mg/ml）and high-dose TEN treatment group （37.5 mg/ml）,each with 15 rats.Model group,low-dose（12.5mg/ml）and high-dose TEN treatment group （37.5 mg/ml）were made by injecting ibotenic acid into Meynertbasal nuclei of aging rat induced by D -gal.At the same time, low-dose TEN treatment group and high-dose TEN treatment group were respectively administrated by gavage for 8 weeks with 12.5mg/ml and 37.5 mg/ml TEN, and the control group was injected with equal volume of normal saline solution instead of D-gal and IBO .The expressions of Ng and pCaMKⅡαin the hippocampus CA 1 area were measured by immunohistochemistry method.Results Compared with the control group , the average absorbance values of Ng and pCaMKⅡαin the model group were decreased significantly （ P〈0.01 ） .Compared with the model group , the average absorbance values of Ng and pCaMKⅡαin low-dose TEN treatment group and high-dose TEN treatment group increased significantly （ P〈0.01 ） .The average absorbance values of Ng and pCaMKⅡαin high-dose TEN treatment group（37.5 mg/ml） increased significantly than in low-dose TEN treatment group（12.5mg/ml）（P〈0.01）. Conclusion TEN can dose-dependently increase the expression of Ng and pCaMKⅡαin the hippocampus CA 1 area of Alzheimer’s disease model rats.