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红曲素的长期疗效——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的应用

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.

作者信息

Fu Pengcheng, Liu Jiachen, Bai Qinqin, Sun Xingang, Yao Zhenjia, Liu Lirong, Wu Cuimei, Wang Gaiqing

机构信息

Department of Neurology, Longhua District Central Hospital, Shenzhen, Guangdong, 187 Guanlan St., 518110, China.

Clinical Medicine, Xiangya Medical College of Central South University, Changsha, Hunan, China.

出版信息

Ther Adv Neurol Disord. 2020 May 14;13:1756286420921083. doi: 10.1177/1756286420921083. eCollection 2020.

Abstract

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.

摘要

背景

血肿是颅内脑出血(ICH)后脑损伤的主要元凶。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ICH中血肿的清除。红曲素作为天然的Nrf2激活剂和PPAR-γ激动剂,ICH后红曲素的长期影响尚未阐明。

方法

通过立体定向、纹状体内注射IV型胶原酶诱导大鼠ICH。ICH诱导后,通过胃灌注每天两次给予红曲素,持续14天。在ICH后7、14和28天评估长期神经功能评分(T迷宫、加西亚评分、转棒试验和莫里斯水迷宫)、血肿体积以及血肿周围的铁过载和脑萎缩情况。

结果

结果表明,红曲素改善了ICH后的长期神经功能缺损、空间记忆表现、学习能力和脑萎缩。红曲素还在ICH后7天减少了血肿体积,并在ICH后7天和14天降低了铁含量。

结论

PPARγ和Nrf2在大鼠ICH后的血肿清除中起关键作用。作为PPARγ和Nrf2的双重激动剂,红曲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,改善了长期预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5b0/7232052/f9e045c19dc3/10.1177_1756286420921083-fig1.jpg

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