Lyu YanXia, Tu HanJun, Luo Jie, Wang ChaoJia, Li AnRong, Zhou Yi, Zhao JunShuang, Wang Hui, Hu JunTao
Department of Physiology, Hubei University of Medicine, Shiyan, Hubei Province, China.
Department of Neurosurgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei Province, China.
Brain Res. 2024 Apr 1;1828:148759. doi: 10.1016/j.brainres.2024.148759. Epub 2024 Jan 17.
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.
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).
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.
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.
炎症相关因子在颅内动脉瘤（IA）的起始、进展和破裂过程中起关键作用。高迁移率族蛋白B1（HMGB - 1）作为一种警报信号，推动炎症性疾病的发病机制。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。
共有28只成年雄性日本白兔被纳入研究，其中包括弹力酶诱导动脉瘤组（n = 18）和对照组（正常兔，n = 10）。为评估HMGB - 1的表达，对取自人类受试者（10例IA患者和10名健康供体）以及兔（动脉瘤组和对照组）的血清样本进行逆转录聚合酶链反应（RT - PCR）和酶联免疫吸附测定（ELISA）。采用免疫组织化学和免疫荧光法评估弹性纤维、HMGB - 1、肿瘤坏死因子 - α（TNF - α）和髓系细胞触发受体 - 1（TREM - 1）的表达水平。
发现IA组中HMGB - 1的表达在mRNA和蛋白水平均显著高于对照组（P < 0.0001）。与对照组相比，兔动脉瘤模型组也观察到类似结果（P < 0.0001）。与外壁相比，HMGB - 1表达在动脉瘤内壁更为丰富，而在对照组中则很少散在分布。此外，TNF - α和TREM - 1的定位模式与HMGB - 1表现出相似特征。
我们的研究结果表明，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相似的定位模式表明它们可能参与了与IA相关的炎症过程。这些结果突出了HMGB - 1作为IA新型治疗靶点的潜力。
