Zhong Shu-Zhi, ma Shi-Ping, Hong Zong-Yuan
Department of Histology and Embryology, Wannan Medical College, Wuhu 241002, China.
Yao Xue Xue Bao. 2013 Aug;48(8):1353-7.
This study was to investigate the effect of peoniflorin on the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream signal molecules in the hippocampus of Alzheimer's disease (AD) rats for exploring the mechanism of peoniflorin protecting hippocampal neurons. AD model rats were established by bilateral intrahippocampal injection of beta-amyloid(1-42) (Abeta(1-42)) and divided randomly into 3 groups: AD model group, peoniflorin low-dose (15 mg x kg(-1)) group and peoniflorin high-dose (30 mg x kg(-1)) group. The vehicle control rats were given bilateral intrahippocampal injection of solvent with the same volume. After peoniflorin or saline was administered (ip) once daily for 14 days, the hippocampuses of all animals were taken out for measuring the expressions of Nrf2, heme oxygenase-1 (HO-1) and gamma-glutamylcysteine synthethase (gamma-GCS) mRNA by reverse transcription PCR, determining the contents of glutathione (GSH), malondialdehyde (MDA) and carbonyl protein (CP) using colorimetric method, and for assaying the expressions of neuronal apoptosis inhibitory protein (NAIP) and Caspase-3 by immunohistochemical staining method. The results showed that peoniflorin markedly increased the expressions of Nrf2, HO-1 and gamma-GCS mRNA, enhanced the level of GSH and decreased the contents of MDA and CP in the hippocampus, as compared with the model group. Peoniflorin also improved the NAIP expression and reduced the Caspase-3 expression in the hippocampus neurons. In conclusion, peoniflorin protects against the Abeta(1-42)-mediated oxidative stress and hippocampal neuron injury in AD rats by activating the Nrf2/ARE pathway.
本研究旨在探讨芍药苷对阿尔茨海默病(AD)大鼠海马中核因子红细胞2相关因子2(Nrf2)及其下游信号分子表达的影响,以阐明芍药苷保护海马神经元的机制。通过双侧海马内注射β-淀粉样蛋白(1-42)(Aβ(1-42))建立AD模型大鼠,并随机分为3组:AD模型组、芍药苷低剂量(15 mg·kg⁻¹)组和芍药苷高剂量(30 mg·kg⁻¹)组。对假手术对照组大鼠双侧海马内注射相同体积的溶剂。芍药苷或生理盐水每日腹腔注射给药14天后,取出所有动物的海马,采用逆转录PCR法检测Nrf2、血红素加氧酶-1(HO-1)和γ-谷氨酰半胱氨酸合成酶(γ-GCS)mRNA的表达,采用比色法测定谷胱甘肽(GSH)、丙二醛(MDA)和羰基蛋白(CP)的含量,采用免疫组织化学染色法检测神经元凋亡抑制蛋白(NAIP)和半胱天冬酶-3(Caspase-3)的表达。结果显示,与模型组相比,芍药苷显著增加了海马中Nrf2、HO-1和γ-GCS mRNA的表达,提高了GSH水平,降低了MDA和CP的含量。芍药苷还改善了海马神经元中NAIP的表达,降低了Caspase-3的表达。综上所述,芍药苷通过激活Nrf2/ARE途径保护AD大鼠免受Aβ(1-42)介导的氧化应激和海马神经元损伤。