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促进慢性硬膜下血肿大鼠模型中缺氧诱导因子1的降解以及抗血管生成和抗炎作用

Promotes the Degradation of Hypoxia-Inducible Factor 1 and Antiangiogenesis and Anti-Inflammation in Chronic Subdural Hematoma Rat Model.

作者信息

Liu Jialin, Dong Xiaoke, Li Zhonghao, Wang Gesheng, Zhou Yujia, Liu Chongchong, Wang Kaiyue, Li Lili, Liu Jinmin

机构信息

Department of Neurosurgery, Dongfang Hospital Beijing University of Chinese Medicine, Beijing 100078, China.

Department of Neurology, Dongfang Hospital Beijing University of Chinese Medicine, Beijing 100078, China.

出版信息

Evid Based Complement Alternat Med. 2020 Apr 6;2020:2305017. doi: 10.1155/2020/2305017. eCollection 2020.

DOI:10.1155/2020/2305017
PMID:32328124
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7165346/
Abstract

(XYK) is a Chinese patent medicine approved by the National Medical Product Administration which is used to treat intracranial hematoma in China. In this study, we observed the molecular mechanism of XYK in hypoxia-inducible factor 1 (HIF-1), inflammation and angiogenesis of chronic subdural hematoma (CSDH). The CSDH model was made by using internal iliac vein blood of Wister rats, and rats were divided into sham group, CSDH group and XYK group. The rats in the XYK group were gavaged with (185 mg/kg) for 7 days, and rats in the CSDH group and sham group were gavaged with the same amount of physiological saline for 7 days. In the CSHD rat model, active inflammation and angiogenesis were observed around the hematoma. XYK promoted the ubiquitination and degradation of HIF-1, and reduced the concentration of VEGF and the ratio of angiopoietin-1/angiopoietin-2. XYK reduced proinflammatory cytokines and increased anti-inflammatory cytokine. In tissue section, XYK reduced the size of the hematoma and membrane, and reduced vWF positive cells in membrane. Furthermore, the endothelial progenitor cells in blood decreased as well. Overall, XYK shows anti-inflammatory and antiangiogenesis effects which may relate to the degradation of HIF-1.

摘要

醒脑再造胶囊(XYK)是一种经国家药品监督管理局批准的用于治疗颅内血肿的中成药。在本研究中,我们观察了醒脑再造胶囊对慢性硬膜下血肿(CSDH)缺氧诱导因子1(HIF-1)、炎症和血管生成的分子机制。采用Wister大鼠髂内静脉血制作CSDH模型,并将大鼠分为假手术组、CSDH组和醒脑再造胶囊组。醒脑再造胶囊组大鼠给予185mg/kg药物灌胃7天,CSDH组和假手术组大鼠给予等量生理盐水灌胃7天。在CSDH大鼠模型中,血肿周围观察到活跃的炎症和血管生成。醒脑再造胶囊促进HIF-1的泛素化和降解,降低血管内皮生长因子(VEGF)浓度和血管生成素-1/血管生成素-2的比值。醒脑再造胶囊降低促炎细胞因子水平,增加抗炎细胞因子水平。在组织切片中,醒脑再造胶囊减小了血肿和包膜的大小,并减少了包膜中血管性血友病因子(vWF)阳性细胞。此外,血液中的内皮祖细胞也减少了。总体而言,醒脑再造胶囊具有抗炎和抗血管生成作用,这可能与HIF-1的降解有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7b6/7165346/a20ac641afb1/ECAM2020-2305017.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7b6/7165346/7fe7e536c1a4/ECAM2020-2305017.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7b6/7165346/a4f4c03261a8/ECAM2020-2305017.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7b6/7165346/05d5175afb2b/ECAM2020-2305017.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7b6/7165346/b11f5a9278f5/ECAM2020-2305017.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7b6/7165346/a20ac641afb1/ECAM2020-2305017.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7b6/7165346/7fe7e536c1a4/ECAM2020-2305017.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7b6/7165346/a4f4c03261a8/ECAM2020-2305017.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7b6/7165346/05d5175afb2b/ECAM2020-2305017.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7b6/7165346/b11f5a9278f5/ECAM2020-2305017.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7b6/7165346/a20ac641afb1/ECAM2020-2305017.005.jpg

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本文引用的文献

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Safety and Efficacy of Atorvastatin for Chronic Subdural Hematoma in Chinese Patients: A Randomized ClinicalTrial.阿托伐他汀治疗中国慢性硬膜下血肿患者的安全性和有效性:一项随机临床试验。
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World Neurosurg. 2018 Aug;116:402-411.e2. doi: 10.1016/j.wneu.2018.05.037. Epub 2018 May 14.
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Parkin targets HIF-1α for ubiquitination and degradation to inhibit breast tumor progression.
帕金通过泛素化和降解 HIF-1α 抑制乳腺癌进展。
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Role of Matrix Metalloproteinase-2, Matrix Metalloproteinase-9, and Vascular Endothelial Growth Factor in the Development of Chronic Subdural Hematoma.基质金属蛋白酶-2、基质金属蛋白酶-9和血管内皮生长因子在慢性硬膜下血肿形成中的作用
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