藏红花素调控Nrf2/HO-1通路改善血管性认知障碍大鼠学习记忆能力实验研究

目的:探讨藏红花素对血管性认知障碍(VCI)大鼠学习记忆能力的影响及机制。方法:通过反复夹闭双侧颈总动脉建立VCI大鼠模型,假手术组暴露双侧颈总动脉但不夹闭; 将VCI模型大鼠随机分为模型组、藏红花素低剂量组(10 mg/kg)、藏红花素中剂量组(20 mg/kg)、藏红花素高剂量组(40 mg/kg)和多奈哌齐组(0.5 mg/kg)。连续给药4周后,评测大鼠学习能力和记忆能力,观察海马体CA1区病理性变化和神经元凋亡状况; 检测海马体CA1区氧化应激指标和炎症因子水平,Western blot法检测核因子E2相关因子2(Nrf2)、血红素氧合酶1(HO-1)、核因子-κB(NF-κB)蛋白表达。结果:藏红花素或多奈哌齐治疗4周可提高VCI大鼠学习能力和记忆能力,改善海马体CA1区病变和神经元凋亡状况,提高超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力,降低丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)水平,上调Nrf2、HO-1表达,下调NF-κB表达(P<0.05)。上述指标除GSH-Px活力和MDA、IL-1β水平外,藏红花素对其他指标的作用均表现出剂量依赖性; 除GSH-Px活力、IL-1β水平外,藏红花素高剂量对其他指标的作用优于多奈哌齐(P<0.05)。结论:藏红花素可能通过激活Nrf2/HO-1通路降低海马体氧化应激损伤,对VCI大鼠学习记忆能力有改善作用。

Research of Crocin improved learning and memory ability in vascular cognitive impairment rats by regulating Nrf2/HO-1 pathway

Objective:To investigate the effect of Crocin on the learning and memory ability of vascular cognitive impairment(VCI)rats and related mechanisms.Methods:The VCI rat model was established by repeatedly clipping the bilateral common carotid arteries,and the sham operation group exposed the bilateral common carotid arteries without clipping.The VCI model rats were randomly divided into the model group,low-dose Crocin group(10 mg/kg),middle-dose Crocin group(20 mg/kg),high-dose Crocin group(40 mg/kg)and donepezil group(0.5 mg/kg).After continuous administration for 4 weeks,the learning ability and memory ability were evaluated,the pathological changes and neuronal apoptosis in the CA1 region of the hippocampus were observed,the level of oxidative stress indexes and inflammatory factors in the CA1 region of the hippocampus were detected.The proteins expression of Nrf2,HO-1 and nuclear factor-κB(NF-κB)were detected by Western blotting method.Results:Crocin or donepezil treatment for 4 weeks could improve the learning ability and memory ability of VCI rats,improve hippocampal CA1 area lesions and neuronal apoptosis to varying degrees,increase the activity of SOD and GSH-Px,decrease the content of MDA,TNF-α,IL-1β,up-regulate the expression of Nrf2 and HO-1,down-regulate the expression of NF-κB,all of the difference was statistically significant(P<0.05).Except for MDA content,GSH-Px activity and IL-1β level,there showed a dose-dependent improvement effect of crocin on other indicators.Except for GSH-Px activity and IL-1β level,the effect of high-dose Crocin group on other indicators were better than that of donepezil group(P<0.05).Conclusion:Crocin may reduce oxidative stress injury in hippocampus by activating Nrf2/HO-1 pathway,and improve learning and memory ability of VCI rats.