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六氢姜黄素减轻脑缺血/再灌注大鼠血脑屏障功能障碍。

Hexahydrocurcumin alleviated blood-brain barrier dysfunction in cerebral ischemia/reperfusion rats.

机构信息

Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.

Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.

出版信息

Pharmacol Rep. 2020 Jun;72(3):659-671. doi: 10.1007/s43440-019-00050-9. Epub 2020 Jan 13.

Abstract

BACKGROUND

Hexahydrocurcumin (HHC), a major metabolite of curcumin, has been reported to have protective effects against ischemic and reperfusion damage. The goal of the present research was to examine whether HHC could alleviate brain damage and ameliorate functional outcomes by diminishing the blood-brain barrier (BBB) damage that follows cerebral ischemia/reperfusion.

METHODS

Middle cerebral artery occlusion was induced for 2 h in rats followed by reperfusion. The rats were divided into three groups: sham-operated, vehicle-treated, and HHC-treated groups. At the onset of reperfusion, the rats were immediately intraperitoneally injected with 40 mg/kg HHC. At 48 h after reperfusion, the rats were evaluated for neurological deficits and TTC staining. At 24 h and 48 h after reperfusion, animals were sacrificed, and their brains were extracted.

RESULTS

Treatment with HHC reduced neurological scores, infarct volume, morphological changes, Evans blue leakage and immunoglobulin G extravasation. Moreover, HHC treatment reduced BBB damage and neutrophil infiltration, downregulated myeloperoxidase, ICAM-1, and VCAM-1, upregulated tight junction proteins (TJPs), and reduced aquaporin 4 expression and brain water content.

CONCLUSION

These results revealed that HHC treatment preserved the BBB from cerebral ischemia/reperfusion injury by regulating TJPs, attenuating neutrophil infiltration, and reducing brain edema formation.

摘要

背景

六氢姜黄素(HHC)是姜黄素的主要代谢物,据报道具有抗缺血再灌注损伤的保护作用。本研究的目的是研究 HHC 是否可以通过减轻脑缺血/再灌注后血脑屏障(BBB)损伤来减轻脑损伤和改善功能结果。

方法

在大鼠中诱导 2 小时大脑中动脉闭塞,然后再灌注。大鼠分为三组:假手术组、载体处理组和 HHC 处理组。再灌注开始时,大鼠立即腹腔注射 40mg/kg HHC。再灌注后 48 小时,对大鼠进行神经功能缺损和 TTC 染色评估。再灌注后 24 小时和 48 小时处死动物,提取其大脑。

结果

HHC 治疗可降低神经评分、梗死体积、形态变化、伊文思蓝渗漏和免疫球蛋白 G 渗出。此外,HHC 治疗可减轻 BBB 损伤和中性粒细胞浸润,下调髓过氧化物酶、ICAM-1 和 VCAM-1,上调紧密连接蛋白(TJPs),并降低水通道蛋白 4 的表达和脑含水量。

结论

这些结果表明,HHC 治疗通过调节 TJPs、减轻中性粒细胞浸润和减少脑水肿形成来保护 BBB 免受脑缺血/再灌注损伤。

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