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黄芪多糖(APS)通过调节三磷酸腺苷(ATP)/嘌呤能受体(P2X7R)轴增强 M2 小胶质细胞极化,发挥对急性缺血性脑卒中(AIS)的保护作用。

Astragalus polysaccharide (APS) exerts protective effect against acute ischemic stroke (AIS) through enhancing M2 micoglia polarization by regulating adenosine triphosphate (ATP)/ purinergic receptor (P2X7R) axis.

机构信息

Department of Neurology, Guangzhou Hospital of Integrated Traditional and West Medicine, Guangzhou, China.

Nursing Department, Guangzhou Hospital of Integrated Traditional and West Medicine, Guangzhou, China.

出版信息

Bioengineered. 2022 Feb;13(2):4468-4480. doi: 10.1080/21655979.2021.1980176.

DOI:10.1080/21655979.2021.1980176
PMID:35166175
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8973874/
Abstract

Clinically, the effective treatment for patients with acute ischemic stroke (AIS) is very limited. Therefore, this paper aims to investigate the mechanism how astragalus polysaccharide (APS) exerts protective effect against AIS and provide a new method for the treatment of AIS. Cell surface antigen flow cytometry and immunofluorescence were used to identify M1 and M2 microglia. Western blot was used to evaluate the expression of associated protein. Oxygen-glucose deprivation (OGD) was used to simulate the effect of AIS on rat microglia. The middle cerebral artery occlusion (MCAO) model was established to simulate the effect of AIS . Evans blue dye (EBD) was used to evaluate the permeability of blood-brain barrier (BBB). Western blot and cell surface antigen flow cytometry results showed that APS promoted the M2 polarization of rat microglia by inhibiting the expression of purinergic receptor (P2X7R). APS reversed the effect of OGD on the polarization of rat microglia M1/ M2 by regulating P2X7R. APS reversed the effect of MCAO on the polarization of rat microglia M1/ M2 . Furthermore, APS inhibited the expression of P2X7R by promoting the degradation of adenosine triphosphate (ATP) in the cerebral cortex of MCAO rats. In addition, APS contributed to maintain the integrity of BBB. Summarily, APS can reduce brain injury by promoting the degradation of ATP in microglia and inhibiting the expression of P2X7R after AIS.

摘要

临床上,急性缺血性脑卒中(AIS)患者的有效治疗方法非常有限。因此,本文旨在探讨黄芪多糖(APS)发挥对 AIS 保护作用的机制,并为 AIS 的治疗提供新方法。采用细胞表面抗原流式细胞术和免疫荧光法鉴定 M1 和 M2 小胶质细胞。采用 Western blot 法评估相关蛋白的表达。采用氧葡萄糖剥夺(OGD)模拟 AIS 对大鼠小胶质细胞的作用。建立大脑中动脉闭塞(MCAO)模型模拟 AIS 的作用。采用伊文思蓝染料(EBD)评估血脑屏障(BBB)的通透性。Western blot 和细胞表面抗原流式细胞术结果表明,APS 通过抑制嘌呤能受体(P2X7R)的表达促进大鼠小胶质细胞 M2 极化。APS 通过调节 P2X7R 逆转 OGD 对大鼠小胶质细胞 M1/M2 极化的影响。APS 逆转 MCAO 对大鼠小胶质细胞 M1/M2 极化的影响。此外,APS 通过促进 MCAO 大鼠大脑皮质中三磷酸腺苷(ATP)的降解来抑制 P2X7R 的表达。此外,APS 有助于维持 BBB 的完整性。总之,APS 可通过促进小胶质细胞中 ATP 的降解和抑制 AIS 后 P2X7R 的表达来减轻脑损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d990/8973874/19e7fc92565b/KBIE_A_1980176_F0006_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d990/8973874/c8e8fa835b96/KBIE_A_1980176_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d990/8973874/45e2a2ade2b0/KBIE_A_1980176_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d990/8973874/aab94a89de04/KBIE_A_1980176_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d990/8973874/ba7ce1f8afdc/KBIE_A_1980176_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d990/8973874/dc7a63d11991/KBIE_A_1980176_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d990/8973874/19e7fc92565b/KBIE_A_1980176_F0006_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d990/8973874/c8e8fa835b96/KBIE_A_1980176_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d990/8973874/45e2a2ade2b0/KBIE_A_1980176_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d990/8973874/aab94a89de04/KBIE_A_1980176_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d990/8973874/ba7ce1f8afdc/KBIE_A_1980176_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d990/8973874/dc7a63d11991/KBIE_A_1980176_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d990/8973874/19e7fc92565b/KBIE_A_1980176_F0006_B.jpg

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