芹菜素通过激活Nrf2/HO-1通路改善血管性痴呆大鼠的认知功能

[目的]研究芹菜素(APG)对血管性痴呆(VD)大鼠认知功能的保护作用及机制。[方法]通过结扎双侧颈总动脉复制VD大鼠模型，设置假手术组、模型组、APG低剂量组、APG高剂量组和尼莫地平(NMP)组，每组30只。APG低剂量组、高剂量组分别1次/天腹腔注射20、40 mg/kg APG,NMP组1次/天腹腔注射2 mg/kg NMP,假手术组和模型组给予生理盐水，疗程28天。Morris水迷宫实验检测大鼠的认知功能，HE染色和TUNEL染色观察海马体CA1区神经元病理特点和凋亡状况，通过电子显微镜观察神经元超微结构变化，分光光度法检测海马体丙二醛(MDA)含量和超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性；RT-PCR和Western blot检测海马体核因子E2相关因子2(Nrf2)、血红素加氧酶1(HO-1)mRNA和蛋白的表达。[结果]与模型组相比，APG高剂量组和NMP组大鼠的认知功能明显改善；海马体CA1区神经元数量、形态结构病理学改变、超微结构改变和凋亡状况均明显改善，病理分级和凋亡指数(AI)降低；海马体MDA含量降低，SOD、GSH-Px活性升高，N...

Apigenin improves cognitive function in vascular dementia rats by activating Nrf2/HO-1 pathway

Aim To investigate the protective effect and mechanism of apigenin (APG) on cognitive function in vascular dementia (VD) rats. Methods The VD rat model was replicated by ligating bilateral common carotid arteries, and the sham group, model group, APG low-dose group, APG high-dose group, nimodipine (NMP) group were setted, with 30 rats in each group. The rats in APG low-dose group and high-dose group were administered intraperitoneally once a day at doses of 0,0 mg/kg APG respectively, the rats in the NMP group were administered intraperitoneally once a day at doses of 2 mg/kg NMP, the rats in the sham group and model group were given normal saline, the course of treatment was 28 days. The cognitive function was detected by Morris water maze test, the pathological characteristics and apoptosis of neurons in the CA1 region of the hippocampus were observed through HE staining and TUNEL staining, the ultrastructural changes of neurons was observed by electron microscopy. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in hippocampal were detected by spectrophotometric method. The mRNA and protein expression of nuclear factor E2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were detected by RT-PCR and Western blot. Results Compared with the model group, the cognitive function was significantly improved of rats in the APG high-dose group and NMP group; the number of neurons of hippocampus CA1 area, morphological and structural pathological changes, ultra-micromorphological changes and apoptosis were significantly improved, the pathological grade and apoptosis index (AI) were reduced; the content of MDA in the hippocampus was decreased, and the activity of SOD, GSH-Px were increased; the mRNA and protein expression of Nrf2, HO-1 were increased. The APG high-dose group had better effects on all indicators than those of NMP group. ConclusionAPG can significantly improve the cognitive function of VD rats, which may be related to the activating Nrf2/HO-1 pathway by APG, inhibiting oxidative stress and reducing brain hippocampus damage.