Expression and significance of tumor necrosis factor alpha, nuclear factor kappaB and ionized calcium binding adaptor molecule-1 in the hippocampus of mice with aortic dissection

doi:10.12307/2025.958

Abstract

Abstract: BACKGROUND: Hippocampal injury caused by aortic coarctation has been poorly studied, and combined detection of tumor necrosis factor α, nuclear factor κB and ionized calcium binding adaptor molecule-1 expression in aortic dissection has not been reported.
OBJECTIVE: To observe histomorphologic changes in the hippocampus of a mouse model of aortic dissection and investigate the expression and significance of tumor necrosis factor alpha, nuclear factor kappaB and ionized calcium binding adaptor molecule-1 in the hippocampus of aortic dissection mice.
METHODS: Sixteen healthy 3-week-old male C57BL/6 mice were randomly divided into two groups: control group and aortic dissection group, with eight mice in each group. In the aortic dissection group, mice were given β-aminopropionitrile monofumarate as drinking water for 4 weeks, and the angiotensin II microinfiltration pump was then implanted to establish an animal model of aortic dissection. Mice in the control group were given normal diet and water. After the model was established, the maximum diameter of the ascending aorta was measured, hematoxylin-eosin staining and EVG staining were performed to evaluate the model formation rate, and the levels of inflammatory factors tumor necrosis factor α and interleukin 6 in serum were detected by enzyme-linked immunosorbent assay. The hippocampus was dissected and stained with hematoxylin-eosin to observe the pathological changes of the hippocampus in brain sections. The protein expression of tumor necrosis factor α, nuclear factor κB and ionized calcium binding adaptor molecule-1 was detected by western blot analysis.
RESULTS AND CONCLUSION: (1) Compared with the control group, the maximum diameter of the ascending aorta in the aortic dissection group was significantly enlarged. (2) Hematoxylin-eosin staining of the aorta showed obvious thickening of the middle aorta and destruction and disorder of the aortic wall structure in mice. Neurons in the CA1 and CA3 regions of mice were sparsely arranged, reduced in size, and showed pyknosis with deeply stained nuclei. (3) Serum levels of inflammatory factors tumor necrosis factor α and interleukin 6 were increased in the aortic dissection group compared with the control group (P < 0.01). (4) The expression levels of tumor necrosis factor α, nuclear factor κB, phosphorylated nuclear factor κB, and ionized calcium binding adaptor molecule-1 in the hippocampus were increased in the aortic dissection group compared with the control group (P < 0.05). To conclude, microglial activation and increased expression of tumor necrosis factor α and nuclear factor κB may be involved in hippocampal neuron injury in aortic dissection mice.

Key words: aortic dissection, hippocampus, neurons, tumor necrosis factor α, ionized calcium binding adaptor molecule-1, engineered tissue construction

CLC Number:

Ma Hong, Ding Xueling, Wang Qi, Lyu Hui, Asya Albusm, Cheng Xinyi, Ma Xiang. Expression and significance of tumor necrosis factor alpha, nuclear factor kappaB and ionized calcium binding adaptor molecule-1 in the hippocampus of mice with aortic dissection[J]. Chinese Journal of Tissue Engineering Research, 2026, 30(4): 858-863.

Figures/Tables 4

2.1 实验动物数量分析将实验选用的16只小鼠分为2组。直到实验结束，正常对照组无夹层形成及死亡情况；主动脉夹层组仍存活小鼠中4只形成主动脉夹层，2只小鼠主动脉夹层破裂死亡，2只小鼠未形成，小鼠主动脉夹层成模率为75%，破裂率为 25%。2只死亡的小鼠，第1只发生在造模第24天，第2只在埋泵后1周内、第33天死亡。 2.2 小鼠胸主动脉夹层成瘤及破裂情况采用小动物超声仪在小鼠埋泵3 d后测量对照组和主动脉夹层组小鼠的主动脉直径，采集小鼠升主动脉及腹主动脉的相关指标，根据升主动脉最大直径是否扩张来分析主动脉夹层发生情况(图1A)。从小鼠主动脉解剖宏观图上看，主动脉夹层组小鼠主动脉撕裂、血肿及破口形成(图1B)。死亡小鼠立即解剖，观察到主动脉夹层组胸腔大量血凝块，判定为夹层破裂致死(图1C)。与对照组相比，主动脉夹层组形成夹层小鼠的主动脉直径明显扩张，并且有统计学意义(图1D)。 2.3 小鼠主动脉病理变化在光学显微镜下观察两组小鼠主动脉苏木精-伊红染色和EVG病理染色结果，如图2所示，发现对照组小鼠主动脉壁结构均完整，未见明显增厚及炎性细胞浸润；而主动脉夹层组小鼠主动脉中层明显增厚，并可见主动脉壁结构破坏、弹性纤维断裂。 2.4 小鼠血清中炎症指标肿瘤坏死因子α和白细胞介素6的表达水平用ELISA试剂盒检测结果显示，与对照组小鼠相比，经过β-氨基丙腈联合血管紧张素Ⅱ干预的主动脉夹层组小鼠血清肿瘤坏死因子α和白细胞介素6表达水平均有所增加，且差异有显著性意义(图3)。 2.5 小鼠海马病理变化在光学显微镜下观察两组小鼠海马体苏木精-伊红染色情况，如图4所示，发现对照组小鼠海马神经元细胞排列整齐致密，形态结构正常；主动脉夹层组CA1和CA3区海马神经元排列疏松，神经元细胞变性坏死，神经元数目减少，核固缩深染，核碎裂。 2.6 小鼠海马肿瘤坏死因子α、核因子κB、磷酸化核因子κB及Iba-1蛋白的表达蛋白免疫印迹结果显示，与对照组相比，主动脉夹层小鼠海马组织肿瘤坏死因子α、核因子κB、磷酸化核因子κB及Iba-1蛋白表达水平均显著升高(P < 0.05或P < 0.01)，见图5。结果提示主动脉夹层小鼠海马损伤，小胶质细胞活化，肿瘤坏死因子α、核因子κB和磷酸化核因子κB蛋白参与神经细胞损伤引起的炎症反应过程。"

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