Abstract：
BACKGROUND: Myocardial ischemia-reperfusion (MI/R) can lead to structural and functional abnormalities in the hippocampal neurons of the brain. High-mobility group box-l (HMGB1) is implicated in the activation of immune cells and the stimulation of inflammatory responses. However, the specific role of HMGB1 in cognitive impairment induced by MI/R in elderly rats has yet to be elucidated.
METHODS: Elderly rats underwent surgical procedures to induce MI/R. To evaluate the learning and memory abilities of these rats, a water maze test and a new-object recognition test were administered. Nissl staining was utilised to examine hippocampal neuron damage. Enzyme-linked immunosorbent assay, western blotting, and real-time quantitative polymerase chain reaction (RT-qPCR) analyses were conducted to measure the expression levels of HMGB1, inflammatory cytokines, and molecular pathways.
RESULTS: The study found that MI/R induced cognitive impairment in elderly rats. There was an observed increase in serum HMGB1 levels, along with elevated concentrations of pro-inflammatory cytokines in the plasma and hippocampus, accompanied by a decrease in anti-inflammatory cytokines. Moreover, substantial damage was evident in the hippocampal neurons of rats exposed to MI/R. In the brains of these rats, there was an increased expression of HMGB1, the receptor for advanced glycation end products (RAGE), toll-like receptor 4 (TLR4), phosphorylated p65, interleukin-1β (IL-1β), IL-6, IL-23, tumour necrosis factor-α (TNF-α), caspase-3, and Bax. In contrast, the expression of B-cell lymphoma 2 was decreased. The RT-qPCR analyses indicated elevated levels of HMGB1, RAGE, TLR4, IL-1β, IL-6, IL-23, TNF-α, caspase-3, and Bax mRNA.
CONCLUSIONS: The increased concentration of serum and hippocampal inflammatory factors in the brains of elderly rats subjected to MI/R suggests that cognitive impairment may be induced through the activation of the HMGB1/TLR4/NF-κB signalling pathway.
METHODS: Elderly rats underwent surgical procedures to induce MI/R. To evaluate the learning and memory abilities of these rats, a water maze test and a new-object recognition test were administered. Nissl staining was utilised to examine hippocampal neuron damage. Enzyme-linked immunosorbent assay, western blotting, and real-time quantitative polymerase chain reaction (RT-qPCR) analyses were conducted to measure the expression levels of HMGB1, inflammatory cytokines, and molecular pathways.
RESULTS: The study found that MI/R induced cognitive impairment in elderly rats. There was an observed increase in serum HMGB1 levels, along with elevated concentrations of pro-inflammatory cytokines in the plasma and hippocampus, accompanied by a decrease in anti-inflammatory cytokines. Moreover, substantial damage was evident in the hippocampal neurons of rats exposed to MI/R. In the brains of these rats, there was an increased expression of HMGB1, the receptor for advanced glycation end products (RAGE), toll-like receptor 4 (TLR4), phosphorylated p65, interleukin-1β (IL-1β), IL-6, IL-23, tumour necrosis factor-α (TNF-α), caspase-3, and Bax. In contrast, the expression of B-cell lymphoma 2 was decreased. The RT-qPCR analyses indicated elevated levels of HMGB1, RAGE, TLR4, IL-1β, IL-6, IL-23, TNF-α, caspase-3, and Bax mRNA.
CONCLUSIONS: The increased concentration of serum and hippocampal inflammatory factors in the brains of elderly rats subjected to MI/R suggests that cognitive impairment may be induced through the activation of the HMGB1/TLR4/NF-κB signalling pathway.
摘要：
背景：心肌缺血再灌注（MI/R）可导致大脑海马神经元的结构和功能异常。高迁移率族蛋白盒-1(HMGB1)与免疫细胞的激活和炎症反应的刺激有关。然而,HMGB1在老年大鼠MI/R所致认知障碍中的具体作用尚未阐明。
方法：老年大鼠接受外科手术诱导MI/R。为了评估这些大鼠的学习和记忆能力，进行了水迷宫测试和新物体识别测试。利用Nissl染色检查海马神经元损伤。酶联免疫吸附测定,西方印迹,和实时定量聚合酶链反应（RT-qPCR）分析，以测量HMGB1，炎症细胞因子的表达水平，和分子途径。
结果：研究发现MI/R可引起老年大鼠认知功能损害。观察到血清HMGB1水平升高，随着血浆和海马中促炎细胞因子浓度的升高，伴随着抗炎细胞因子的减少。此外，暴露于MI/R的大鼠海马神经元明显损伤。在这些老鼠的大脑中，晚期糖基化终产物（RAGE）受体HMGB1的表达增加，toll样受体4（TLR4），磷酸化p65，白细胞介素-1β（IL-1β），IL-6、IL-23、肿瘤坏死因子-α(TNF-α)、caspase-3和Bax。相比之下,B细胞淋巴瘤2的表达降低。RT-qPCR分析表明HMGB1，RAGE，TLR4,IL-1β,IL-6，IL-23，TNF-α，caspase-3和BaxmRNA。
结论：老年MI/R大鼠脑内血清和海马炎症因子浓度升高，提示HMGB1/TLR4/NF-κB信号通路的激活可能导致认知障碍。
方法：老年大鼠接受外科手术诱导MI/R。为了评估这些大鼠的学习和记忆能力，进行了水迷宫测试和新物体识别测试。利用Nissl染色检查海马神经元损伤。酶联免疫吸附测定,西方印迹,和实时定量聚合酶链反应（RT-qPCR）分析，以测量HMGB1，炎症细胞因子的表达水平，和分子途径。
结果：研究发现MI/R可引起老年大鼠认知功能损害。观察到血清HMGB1水平升高，随着血浆和海马中促炎细胞因子浓度的升高，伴随着抗炎细胞因子的减少。此外，暴露于MI/R的大鼠海马神经元明显损伤。在这些老鼠的大脑中，晚期糖基化终产物（RAGE）受体HMGB1的表达增加，toll样受体4（TLR4），磷酸化p65，白细胞介素-1β（IL-1β），IL-6、IL-23、肿瘤坏死因子-α(TNF-α)、caspase-3和Bax。相比之下,B细胞淋巴瘤2的表达降低。RT-qPCR分析表明HMGB1，RAGE，TLR4,IL-1β,IL-6，IL-23，TNF-α，caspase-3和BaxmRNA。
结论：老年MI/R大鼠脑内血清和海马炎症因子浓度升高，提示HMGB1/TLR4/NF-κB信号通路的激活可能导致认知障碍。
