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Long-term outcomes of monascin - a novel dual peroxisome proliferator-activated receptor γ/nuclear factor-erythroid 2 related factor-2 agonist in experimental intracerebral hemorrhage.
Therapeutic Advances in Neurological Disorders ( IF 5.9 ) Pub Date : 2020-05-14 , DOI: 10.1177/1756286420921083
Pengcheng Fu 1 , Jiachen Liu 2 , Qinqin Bai 3 , Xingang Sun 3 , Zhenjia Yao 3 , Lirong Liu 3 , Cuimei Wu 3 , Gaiqing Wang 4
Affiliation  

Background:

Hematoma is the chief culprit in brain injury following intracranial cerebral hemorrhage (ICH). Noninvasive hematoma clearance could be an option to prevent and alleviate early brain injury after ICH. Peroxisome proliferator-activated receptor γ (PPAR-γ) and nuclear factor-erythroid 2 related factor-2 (Nrf2) facilitate removal of hematoma in ICH. Monascin acts as the natural Nrf2 activator with PPAR-γ agonist, and the long-term effects of monascin following ICH have not been elucidated.

Methods:

ICH in rats was induced by stereotactic, intrastriatal injection of type IV collagenase. Monascin was administered twice daily by gastric perfusion for 14 days after ICH induction. Long-term neurological scores (T maze, Garcia scales, rotor rod test, and Morris water maze), hematoma volume, as well as iron overload around hematoma and brain atrophy were evaluated at 7, 14, and 28 days after ICH.

Results:

The results showed that monascin improved long-term neurological deficits, spatial memory performance, learning ability, and brain shrinkage after ICH. Monascin also reduced hematoma volume at 7 days and iron content at 7 and 14 days after ICH.

Conclusion:

PPAR γ and Nrf2 play a crucial role in hematoma clearance after ICH in rat. As a dual agonist of PPAR γ and Nrf2, monascin improved long-term outcomes by facilitating hematoma clearance, and by attenuating iron overload and brain atrophy after experimental ICH.



中文翻译:

红红霉素的长期结果 - 一种新型双过氧化物酶体增殖物激活受体 γ/核因子 - 红细胞 2 相关因子 2 激动剂在实验性脑出血中。

背景:

血肿是颅内脑出血(ICH)后脑损伤的罪魁祸首。无创血肿清除可能是预防和减轻 ICH 后早期脑损伤的一种选择。过氧化物酶体增殖物激活受体 γ (PPAR-γ) 和核因子 - 红细胞 2 相关因子 2 (Nrf2) 有助于清除 ICH 中的血肿。红红霉素与 PPAR-γ 激动剂一起作为天然 Nrf2 激活剂,红红霉素对 ICH 后的长期影响尚未阐明。

方法:

大鼠 ICH 是通过立体定向、纹状体内注射 IV 型胶原酶诱导的。在 ICH 诱导后,每天两次通过胃灌注给予红红霉素,持续 14 天。在 ICH 后 7、14 和 28 天评估长期神经系统评分(T 迷宫、Garcia 量表、转子棒试验和 Morris 水迷宫)、血肿体积以及血肿周围的铁过载和脑萎缩。

结果:

结果表明,红曲霉素可改善 ICH 后的长期神经功能缺损、空间记忆能力、学习能力和脑萎缩。红红霉素还在 ICH 后 7 天减少血肿体积,并在 7 天和 14 天减少铁含量。

结论:

PPAR γ 和 Nrf2 在大鼠 ICH 后血肿清除中起关键作用。作为 PPAR γ 和 Nrf2 的双重激动剂,红曲霉素通过促进血肿清除以及减轻实验性 ICH 后的铁过载和脑萎缩来改善长期预后。

更新日期:2020-05-14
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