| 金 文,于 巍,王梓鉴,高大鹏,戚思华.心衰大鼠血脑屏障通透性改变对认知功能的影响及机制研究[J].现代生物医学进展英文版,2022,(18):3428-3433. |
| 心衰大鼠血脑屏障通透性改变对认知功能的影响及机制研究 |
| Effects of Altered Blood-brain Barrier Permeability in Heart Failure Rats on Cognitive Function and Its Mechanisms |
| Received:December 23, 2021 Revised:January 25, 2022 |
| DOI：10.13241/j.cnki.pmb.2022.18.005 |
| 中文关键词: 心力衰竭 血脑屏障通透性 认知功能 MMP-9 NF-κB |
| 英文关键词: Heart failure Blood-brain barrier permeability Cognitive function MMP-9 NF-κB |
| 基金项目:国家自然科学基金项目（81271456） |
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| 中文摘要: |
| 摘要 目的：观察大鼠心衰（HF）后血脑屏障通透性的改变，并探讨HF后认知功能障碍的可能机制。方法：本实验采用成年雄性SD大鼠85只，体重300-350 g，将大鼠随机分为5组：假手术组、心力衰竭组、空白对照组、心力衰竭+TAK242组、心力衰竭+抗生素组。造模24 h后采用TTC染色法检测大鼠心肌梗死面积，采用荧光素钠检测血脑屏障通透性的改变，采用蛋白印迹法检测大鼠海马和皮质中炎症蛋白MMP-9与NF-κB表达表达情况。造模4周后采用超声检测大鼠心功能情况，Morris水迷宫法检测大鼠行为学改变，采用HE染色法检测大鼠心脏组织病理学改变。结果：与Sham组相比，HF组大鼠术中循环和血气分析无明显差异（P>0.05）。与Sham组相比，HF组大鼠术后24 h可见清晰的心肌梗死灶，荧光素钠通透性增加，大鼠海马和皮质内炎症蛋白MMP-9与NF-κB表达升高。与HF组比较，给予TAK242的HF组大鼠认知功能得到改善，给予抗生素的HF大鼠认知功能降低。结论：NF-κB /MMP-9炎症通路激活诱导的血脑屏障通透性改变可能是HF后认知功能障碍的作用机制之一。 |
| 英文摘要: |
| ABSTRACT Objective: To observe the changes of blood-brain barrier permeability after heart failure (HF) in rats and explore the possible mechanism of cognitive impairment after HF. Methods: In this experiment, 85 adult male SD rats weighing 300-350 g were randomly divided into 3 groups: sham group, HF group, Control group, HF+TAK242 group, HF+Anti group. After 24 hours of myocardial infarction, myocardial infarct size was measured by TTC staining, the expression of MMP-9 and NF-κB in rat hippocampus and cortex was detected by western blotting, the changes in BBB permeability were detected by sodium fluorescein. After 4 weeks of modeling, the cardiac function of the rats was detected by ultrasound, the behavioral changes of the rats were detected by the Morris water maze method, and the histopathological changes of the rat hearts were detected by the HE staining method. Results: Compared with the sham group, there was no significant difference in intraoperative circulation and blood gas analysis in HF groups (P>0.05). After 24 hours of myocardial infarction, compared with the sham operation group, a clear infarct lesion was observed, and the permeability of sodium fluorescein was increased and the expression levels of MMP-9 and NF-κB in the hippocampus and cortex of the rats were increased in the heart failure group. Compared with the HF group, cognitive function was improved in the HF group given TAK242, and the cognitive function of HF rats given antibiotics was reduced. Conclusion: The change of BBB permeability induced by the activation of NF-κB/ MMP- 9 inflammatory pathway may be one of the mechanisms of cognitive impairment after HF. |
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