| 鲁传豪,李肖亮,孙应辉,曹建华,刘传明.阿司匹林通过调节Hippo途径抑制大鼠颅内动脉瘤的形成和机制[J].,2023,(9):1614-1618 |
| 阿司匹林通过调节Hippo途径抑制大鼠颅内动脉瘤的形成和机制 |
| Aspirin Inhibits the Formation and Mechanism of Intracranial Aneurysms in Rats by Regulating Hippo Pathway |
| 投稿时间：2022-11-04 修订日期：2022-11-28 |
| DOI：10.13241/j.cnki.pmb.2023.09.003 |
| 中文关键词: 颅内动脉瘤 阿司匹林 Hippo途径 炎症 血管内皮损伤 |
| 英文关键词: Intracranial aneurysm Aspirin Hippo pathway Inflammation Vascular endothelial injury |
| 基金项目:陕西省科学技术厅科研基金项目（2019SF-046） |
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| 中文摘要: |
| 摘要 目的：探讨阿司匹林通过调节Hippo途径抑制大鼠颅内动脉瘤形成的机制。方法：选择40只健康SD大鼠分为对照组（不做任何处理）、假手术组（暴露双侧肾动脉后支和左颈总动脉，但不结扎）、动脉瘤组（结扎双侧肾动脉后支和左颈总动脉后生理盐水灌胃）和阿司匹林组（动脉结扎后阿司匹林灌胃），各10只。灌胃12周后检测血清炎性因子[肿瘤坏死因子-α（TNF-α）、单核细胞趋化蛋白-1（MCP-1）、白细胞介素-6（IL-6）、IL-10]、血管内皮损伤标志物[一氧化氮（NO）、内皮素-1（ET-1）、血管内皮生长因子（VEGF）]。处死大鼠后，检测动脉瘤大小、壁厚比、内腔面积和中膜变薄长度，检测动脉瘤血管组织中Yes相关蛋白（YAP）表达情况。结果：（1）动脉瘤组和阿司匹林组大鼠Willis环上有明显凸起，且阿司匹林组大鼠凸起明显小于动脉瘤组。阿司匹林组大鼠动脉瘤大小、内腔面积和中膜变薄长度均显著小于动脉瘤组，壁厚比显著大于动脉瘤组（P＜0.05）。（2）动脉瘤组和阿司匹林组大鼠血清TNF-α、MCP-1、IL-6水平显著高于对照组和假手术组，IL-10水平显著低于对照组和假手术组（P<0.05）；阿司匹林组大鼠血清TNF-α、MCP-1、IL-6水平显著低于动脉瘤组，IL-10水平显著高于动脉瘤组（P<0.05）。（3）动脉瘤组和阿司匹林组大鼠血清NO水平显著低于对照组和假手术组，ET-1和VEGF水平显著高于对照组和假手术组（P<0.05）；阿司匹林组大鼠血清NO水平显著高于动脉瘤组，ET-1和VEGF水平显著低于动脉瘤组（P<0.05）。（4）动脉瘤组和阿司匹林组大鼠YAP蛋白表达相对吸光值显著高于对照组和假手术组（P<0.05）；阿司匹林组大鼠YAP蛋白表达相对吸光值显著低于动脉瘤组（P<0.05）。结论：阿司匹林能够显著减轻颅内动脉瘤大鼠炎性反应，改善血管内皮功能，抑制颅内动脉瘤形成，这可能与阿司匹林调控Hippo信号通路有关。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the mechanism of aspirin inhibiting intracranial aneurysm formation in rats by regulating Hippo pathway. Methods: Forty healthy SD rats were selected and divided into control group (without any treatment), sham operation group (exposing the posterior branches of bilateral renal arteries and left common carotid artery, but without ligation), aneurysm group (perfusing normal saline after ligating the posterior branches of bilateral renal arteries and left common carotid artery) and aspirin group (perfusing aspirin after artery ligation), with 10 rats in each group. Detection of serum inflammatory factors [tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), IL-10)] and vascular endothelial injury markers [nitric oxide (NO), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF)] 12 weeks after intragastric administration. After the rats were killed, the aneurysm size, wall thickness ratio, lumen area and thinning length of the middle membrane were detected. The expression of Yes-associated protein (YAP) was detected. Results: (1) There were obvious bulges on the Willis ring in the aneurysm group and aspirin group, and the bulges in the aspirin group were smaller than those in the aneurysm group. The aneurysm size, lumen area and thinning length of middle membrane in aspirin group were smaller than those in aneurysm group, and the wall thickness ratio was greater than that in aneurysm group (P<0.05). (2) The serum levels of TNF-α, MCP-1 and IL-6 of rats in aneurysm group and aspirin group were higher than those in the control group and sham operation group, while the levels of IL-10 were lower than those in the control group and sham operation group (P<0.05); The serum levels of TNF-α, MCP-1 and IL-6 of rats in aspirin group were lower than those in aneurysm group, while the levels of IL-10 were higher than those in aneurysm group (P<0.05). (3) The levels of serum NO, ET-1 and VEGF in aneurysm group and aspirin group were lower than those in control group and sham operation group (P<0.05); The level of serum NO in aspirin group was higher than that in aneurysm group, and the levels of ET-1 and VEGF were higher than that in aneurysm group (P<0.05). (4) The relative absorbance value of YAP protein expression in aneurysm group and aspirin group was significantly higher than that in control group and sham operation group (P<0.05). The relative light absorption value of YAP protein expression in aspirin group was lower than that in aneurysm group (P<0.05). Conclusion: Aspirin can significantly reduce the inflammatory reaction of rats with intracranial aneurysms, improve vascular endothelial function, and inhibit the formation of intracranial aneurysms, which may be related to the regulation of Hippo signal pathway by inhibiting YAP. |
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