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阿托伐他汀联合地塞米松促进慢性硬膜下血肿优化大鼠模型血肿吸收。

Atorvastatin combined with dexamethasone promote hematoma absorption in an optimized rat model of chronic subdural hematoma.

机构信息

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, Tianjin, China.

Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, Tianjin, China.

出版信息

Aging (Albany NY). 2021 Nov 23;13(22):24815-24828. doi: 10.18632/aging.203717.

Abstract

Previous studies found that atorvastatin and dexamethasone were effective in promoting the absorption of chronic subdural hematoma. In this study, we aimed to investigate the effect of pharmacotherapy in an optimized rat model of chronic subdural hematoma. Rat model of chronic subdural hematoma via a bEnd.3 cell and Matrigel mix was established and dynamic changes in different drug treatment groups were tested. The hematoma gradually increased, peaked on the fifth day (263.8±52.85 μl), and was completely absorbed in two weeks. Notably, Kruppelle-like factor 2 expression was significantly decreased with increasing hematoma volume, and then increased in the repair period. The expression of IL-10 was increased and peaked on 7 days, and then decreased at 14 days. The dynamic trends of IL-6, IL-8, MMP-9, and VEGF were also increased first and then decreased. Both monotherapy and the combined treatment by atorvastatin and dexamethasone could counteract the inflammatory activities, decrease hematoma permeability, and improve hematoma absorption, however, most prominent in combined group. The combined treatment could more effectively increase Kruppelle-like factor 2 and ZO-1 expression, attenuate the expression of NF-κb. Most importantly, the combined treatment enhanced the neural functional prognosis and reduced the mortality of chronic subdural hematoma rats. According to our results, the combined treatment could more effectively attenuate inflammatory. And it could also enhance angiogenic activities which could promote the stability of local function and structure of the hematoma cavity, reduce the hematoma volume and improve the outcomes of rats with chronic subdural hematoma than single treatments in the optimized chronic subdural hematoma model.

摘要

先前的研究发现,阿托伐他汀和地塞米松可有效促进慢性硬膜下血肿的吸收。在本研究中,我们旨在探讨优化后的慢性硬膜下血肿大鼠模型中药物治疗的效果。通过 bEnd.3 细胞和 Matrigel 混合物建立慢性硬膜下血肿大鼠模型,并测试不同药物治疗组的动态变化。血肿逐渐增加,第 5 天(263.8±52.85 μl)达到峰值,并在两周内完全吸收。值得注意的是,Kruppelle 样因子 2 的表达随着血肿体积的增加而显著降低,然后在修复期增加。IL-10 的表达增加,第 7 天达到峰值,然后在第 14 天下降。IL-6、IL-8、MMP-9 和 VEGF 的动态趋势也是先增加后减少。阿托伐他汀和地塞米松的单药治疗和联合治疗均可拮抗炎症活动,降低血肿通透性,促进血肿吸收,但联合治疗效果最为显著。联合治疗可更有效地增加 Kruppelle 样因子 2 和 ZO-1 的表达,减弱 NF-κb 的表达。最重要的是,联合治疗可改善慢性硬膜下血肿大鼠的神经功能预后,降低其死亡率。根据我们的结果,联合治疗可更有效地减轻炎症反应,增强血管生成活性,促进血肿腔局部功能和结构的稳定性,减少血肿体积,改善慢性硬膜下血肿大鼠的预后,优于单一治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95da/8660610/fd9bedc2f512/aging-13-203717-g001.jpg

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