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鞣花酸减轻大鼠脑缺血/再灌注损伤后NLRP6/半胱天冬酶-1/GSDMD介导的炎症和细胞焦亡。

Ellagic acid alleviates NLRP6/caspase-1/GSDMD-mediated inflammation and pyroptosis in rats post cerebral ischemia/reperfusion injury.

作者信息

Hu Ling, Wei Xiaoqiong, Shen Guofu, Huang Xiaohuan

机构信息

Department of Pathology, Chongqing Three Gorges Medical College, Wanzhou, China.

Chongqing Three Gorges Medical College, Wanzhou, China.

出版信息

Iran J Basic Med Sci. 2025;28(1):105-112. doi: 10.22038/ijbms.2024.78864.17057.

DOI:10.22038/ijbms.2024.78864.17057
PMID:39877634
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11771333/
Abstract

OBJECTIVES

Ellagic acid (EA) is a natural polyphenol with anti-cancer, anti-oxidant, anti-inflammatory, antibacterial, and other effects. However, the role of EA in cerebral ischemia/reperfusion injury (CIRI) remains unclear. This study aims to investigate the neuroprotective effects of EA in CIRI.

MATERIALS AND METHODS

Forty male Wistar rats (260-300 g) were randomly divided into four groups with 10 rats per group: 1) Sham+Veh: Rats underwent I/R surgery, except that they were not inserted with thread plugs, and received solute treatment at the same time. 2) MCAO/R+Veh. 3) MCAO/R+EA: Rats were administered 200 mg/kg EA before undergoing MCAO. 4) MCAO/R+Nim: Rats were administered Nim before undergoing MCAO.

RESULTS

Cerebral MCAO/R damaged brain tissue, elevated neurological deficit score (0.01), cerebral infarction volume (0.01), inflammatory cell infiltration (0.01), NLRP6, ASC, caspase-1 and GSDMD mRNA level (0.01 and 0.001), NLRP6, caspase-1, GSDMD-N and IL-1β protein level (0.01 and 0.001), and inflammatory cytokines in brain tissue (0.01). Prophylactic administration of EA also significantly improved brain tissue damage, reduced neurological deficit score (0.01), cerebral infarction volume (0.01), inflammatory cell number (0.05), NLRP6, caspase-1, GSDMD-N mRNA and protein level (0.05 and 0.01), ASC mRNA level and IL-1β protein level (0.01), and IL-1β and IL-18 level in brain tissue (0.01) compared to positive control.

CONCLUSION

EA may serve as a potential drug for the treatment of brain I/R, which may exert an anti-inflammatory effect by inhibiting the activation of the inflammasome.

摘要

目的

鞣花酸(EA)是一种具有抗癌、抗氧化、抗炎、抗菌等作用的天然多酚。然而,EA在脑缺血/再灌注损伤(CIRI)中的作用仍不清楚。本研究旨在探讨EA在CIRI中的神经保护作用。

材料与方法

40只雄性Wistar大鼠(260 - 300 g)随机分为四组,每组10只:1)假手术+溶剂组:大鼠接受缺血/再灌注手术,但未插入线栓,并同时接受溶剂处理。2)大脑中动脉闭塞/再灌注+溶剂组。3)大脑中动脉闭塞/再灌注+EA组:大鼠在大脑中动脉闭塞前给予200 mg/kg EA。4)大脑中动脉闭塞/再灌注+尼莫地平组:大鼠在大脑中动脉闭塞前给予尼莫地平。

结果

大脑中动脉闭塞/再灌注损伤脑组织,升高神经功能缺损评分(P<0.01)、脑梗死体积(P<0.01)、炎性细胞浸润(P<0.01)、NLRP6、ASC、caspase - 1和GSDMD mRNA水平(P<0.01和P<0.001)、NLRP6、caspase - 1、GSDMD - N和IL - 1β蛋白水平(P<0.01和P<0.001)以及脑组织中的炎性细胞因子(P<0.01)。与阳性对照组相比,预防性给予EA还显著改善了脑组织损伤,降低了神经功能缺损评分(P<0.01)、脑梗死体积(P<0.01)、炎性细胞数量(P<0.05)、NLRP6、caspase - 1、GSDMD - N mRNA和蛋白水平(P<0.05和P<0.01)、ASC mRNA水平和IL - 1β蛋白水平(P<0.01)以及脑组织中IL - 1β和IL - 18水平(P<0.01)。

结论

EA可能作为治疗脑缺血/再灌注的潜在药物,其可能通过抑制炎性小体的激活发挥抗炎作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd31/11771333/1a1426c56d87/IJBMS-28-105-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd31/11771333/79b69f9d8dc7/IJBMS-28-105-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd31/11771333/9573f621ed2b/IJBMS-28-105-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd31/11771333/4c56944662d1/IJBMS-28-105-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd31/11771333/cd4d1dfeebe0/IJBMS-28-105-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd31/11771333/8ab460470b70/IJBMS-28-105-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd31/11771333/0689a85a9bb3/IJBMS-28-105-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd31/11771333/1a1426c56d87/IJBMS-28-105-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd31/11771333/79b69f9d8dc7/IJBMS-28-105-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd31/11771333/c7b0d89364c2/IJBMS-28-105-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd31/11771333/9573f621ed2b/IJBMS-28-105-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd31/11771333/4c56944662d1/IJBMS-28-105-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd31/11771333/8ab460470b70/IJBMS-28-105-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd31/11771333/1a1426c56d87/IJBMS-28-105-g008.jpg

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