目的:炎症相关因素在颅内动脉瘤(IA)的发生中起着至关重要的作用,programming,和破裂。高迁移率组盒1(HMGB-1)作为驱动炎性疾病发病机制的警报。本研究旨在评估HMGB-1在IA中的作用,并探讨其与其他炎症相关因子的相关性。
方法:共有28只成年雄性日本白兔纳入弹性蛋白酶诱导的动脉瘤,n=18)和对照组(正常兔,n=10)。为了评估HMGB-1的表达,对从人类受试者(10名IA患者和10名健康供体)获得的血清样品进行逆转录聚合酶链反应(RT-PCR)和酶联免疫吸附测定(ELISA)以及兔(动脉瘤组和对照组)。免疫组织化学和免疫荧光检测弹性纤维的表达水平。HMGB-1,肿瘤坏死因子-α(TNF-α),和在骨髓细胞上表达的触发受体-1(TREM-1)。
结果:发现IA组HMGB-1的表达明显高于对照组,在mRNA和蛋白质水平(P<0.0001)。与对照组相比,在兔动脉瘤模型组中观察到类似的发现(P<0.0001)。观察到HMGB-1在动脉瘤内壁的表达比在外壁的表达更丰富,而在对照组中,它很少分散。此外,TNF-α和TREM-1的定位模式表现出与HMGB-1相似的特征。
结论:我们的发现表明HMGB-1在IA患者和兔动脉瘤模型中均高表达。此外,HMGB-1、TNF-α、和TREM-1提示它们可能参与与IA相关的炎症过程。这些结果突出了HMGB-1作为IA的新型治疗靶标的潜力。
OBJECTIVE: Inflammation-related factors play a crucial role in intracranial aneurysms (IA) initiation, progression, and rupture. High mobility group box 1 (HMGB-1) serves as an alarm to drive the pathogenesis of the inflammatory disease. This study aimed to evaluate the role of HMGB-1 in IA and explore the correlation with other inflammatory-related factors.
METHODS: A total of twenty-eight adult male Japanese white rabbits were included in with elastase-induced aneurysms, n = 18) and the control group (normal rabbits, n = 10). To assess the expression of HMGB-1, both reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) was performed on serum samples obtained from human subjects (10 patients with IA and 10 healthy donors) as well as from rabbits (aneurysm group and control group). Immunohistochemistry and immunofluorescence were employed to evaluate the expression levels of elastic fibers, HMGB-1, tumor necrosis factor-alpha (TNF-α), and triggering receptor expressed on myeloid cells-1 (TREM-1).
RESULTS: The expression of HMGB-1 was found to be significantly higher in the IA group compared to the control group, both at the mRNA and protein levels (P < 0.0001). Similar findings were observed in the rabbit aneurysm model group compared to the control group (P < 0.0001). HMGB-1 expression was observed to be more abundant in the inner wall of the aneurysm compared to the external wall, whereas in the control group, it was rarely scattered. Additionally, the localization patterns of TNF-α and TREM-1 exhibited similar characteristics to HMGB-1.
CONCLUSIONS: Our findings demonstrate that HMGB-1 is highly expressed in both IA patients and rabbit aneurysm models. Furthermore, the similar localization patterns of HMGB-1, TNF-α, and TREM-1 suggest their potential involvement in the inflammatory processes associated with IA. These results highlight the potential of HMGB-1 as a novel therapeutic target for IA.