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[人参皂苷Rg1对冈田酸诱导大鼠脑片tau蛋白磷酸化的影响]

[Effects of gensenoside Rg1 on tau protein phosphorylation induced by okadaic acid in rat brain slices].

作者信息

Li Xi, Liu Ying, Yuan Hai-Feng, Quan Qian-Kun

机构信息

Department of Geriatrics, the Second Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710004, Shaanxi Province, China.

出版信息

Zhong Xi Yi Jie He Xue Bao. 2010 Oct;8(10):955-60. doi: 10.3736/jcim20101007.

Abstract

OBJECTIVE

To investigate the effects of gensenoside Rg1 on expressions of phosphorylated tau protein (P-tau), protein phosphatase 2A (PP2A) and tau protein in Alzheimer's disease-like tau phosphorylation rat brain slices, and to explore the mechanisms of gensenoside Rg1 in inhibiting tau phosphorylation.

METHODS

Brains of 5-week-old Wistar rats were cut into slices which were 400 μm thick. These brain slices were randomly divided into blank control group, untreated group, low-dose ginsenoside Rg1 group, medium-dose ginsenoside Rg1 group and high-dose ginsenoside Rg1 group, with 10 slices in each group. All brain slices were cultured with artificial cerebrospinal fluid (ACSF). And brain slices in the ginsenoside R1 groups were administered with ginsenoside Rg1 (60, 120 and 240 μmol/L respectively) in ACSF for 2 h firstly. After 2-hour culture, okadaic acid (OA) was administered into ACSF of the untreated group and the ginsenoside Rg1 groups separately for 3 h to induce tau phosphorylation to prepare AD models. The concentration of OA in each group was 1 μmol/L. There was no any intervention for the brain slices in the blank control group. Expressions of P-tau, PP2A and tau proteins in the brain slices were determined by immunohistochemical method, and the results were analyzed by image acquisition and analysis system.

RESULTS

Compared with the blank control group, the expression of P-tau protein was significantly increased (P<0.01) and the expressions of tau and PP2A proteins were decreased (P<0.01, P<0.05) in the untreated group. Compared with the untreated group, the expression of P-tau was significantly decreased (P<0.01) and the expressions of tau and PP2A proteins were increased (P<0.01, P<0.05) in the ginsenoside Rg1 groups, especially in the high-dose ginsenoside Rg1 group.

CONCLUSION

Ginsenoside Rg1 can promote dephosphorylation of P-tau by increasing the expression of PP2A in Alzheimer's disease-like tau phosphorylation rat brain slices, so as to inhibit tau phosphorylation.

摘要

目的

研究人参皂苷Rg1对阿尔茨海默病样tau蛋白磷酸化大鼠脑片磷酸化tau蛋白(P-tau)、蛋白磷酸酶2A(PP2A)及tau蛋白表达的影响,探讨人参皂苷Rg1抑制tau蛋白磷酸化的机制。

方法

将5周龄Wistar大鼠的脑切成400μm厚的脑片,随机分为空白对照组、未处理组、低剂量人参皂苷Rg1组、中剂量人参皂苷Rg1组和高剂量人参皂苷Rg1组,每组10片。所有脑片均用人工脑脊液(ACSF)培养,人参皂苷R1组脑片先于含人参皂苷Rg1(分别为60、120和240μmol/L)的ACSF中培养2h。培养2h后,分别向未处理组和人参皂苷Rg1组的ACSF中加入冈田酸(OA)3h以诱导tau蛋白磷酸化制备AD模型,每组OA浓度为1μmol/L。空白对照组脑片不做任何干预。采用免疫组化法检测脑片中P-tau、PP2A及tau蛋白的表达,结果用图像采集与分析系统进行分析。

结果

与空白对照组比较,未处理组P-tau蛋白表达显著升高(P<0.01),tau及PP2A蛋白表达降低(P<0.01,P<0.05)。与未处理组比较,人参皂苷Rg1组P-tau表达显著降低(P<0.01),tau及PP2A蛋白表达升高(P<0.01,P<0.05),尤以高剂量人参皂苷Rg1组明显。

结论

人参皂苷Rg1可通过增加阿尔茨海默病样tau蛋白磷酸化大鼠脑片中PP2A的表达促进P-tau去磷酸化,从而抑制tau蛋白磷酸化。

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