Abstract：
Ischemic stroke is acknowledged as one of the most frequent causes of death and disability, in which neuroinflammation plays a critical role. Emerging evidence supports that the PGK1/Nrf2/HO-1 signaling can modulate inflammation and oxidative injury. Albiflorin (ALB), a main component of Radix paeoniae Alba, possesses anti-inflammatory and antioxidative properties. However, how it exerts a protective role still needs further exploration. In our study, the middle cerebral artery occlusion (MCAO) model was established, and the Longa score was applied to investigate the degree of neurological impairment. Dihydroethidium (DHE) staining and Malondialdehyde (MDA) assay were used to detect the level of lipid peroxidation. 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining was used to measure the infarct area. Evans blue staining was employed to observe the integrality of the blood-brain barrier (BBB). The injury of brain tissue in each group was observed via HE staining. Immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA) and western blot assay were used for the measurement of inflammatory factors and protein levels. We finally observed that ALB relieved cerebral infarction symptoms, attenuated oxidative damage in brain tissues, and reduced neuroinflammation and cell injury in MCAO rats. The overexpression of PGK1 abrogated the protective effect of ALB after experimental cerebral infarction. ALB promoted PGK1 degradation and induced Nrf2 signaling cascade activation for subsequent anti-inflammatory and antioxidant damage. Generally speaking, ALB exerted a protective role in treating cerebral ischemia, and it might target at PGK1/Nrf2/HO-1 signaling. Thus, ALB might be a potential therapeutic agent to alleviate neuroinflammation and protect brain cells after cerebral infarction.
摘要：
缺血性卒中被认为是导致死亡和残疾的最常见原因之一。其中神经炎症起着关键作用。新的证据支持PGK1/Nrf2/HO-1信号传导可以调节炎症和氧化损伤。Albiflorin(ALB),白芍的主要成分，具有抗炎和抗氧化特性。然而,它如何发挥保护作用仍需进一步探索。在我们的研究中,建立大脑中动脉闭塞(MCAO)模型,并应用Longa评分调查神经功能缺损程度。采用二氢乙啶(DHE)染色和丙二醛(MDA)检测脂质过氧化水平。使用2,3,5-氯化三苯基四唑(TTC)染色来测量梗死面积。采用伊文思蓝染色观察血脑屏障(BBB)的完整性。HE染色观察各组脑组织损伤情况。免疫荧光染色,采用酶联免疫吸附试验(ELISA)和免疫印迹法检测炎症因子和蛋白质水平。我们最终观察到ALB缓解了脑梗死症状，减轻脑组织中的氧化损伤，减轻MCAO大鼠的神经炎症和细胞损伤。PGK1的过表达消除了实验性脑梗死后ALB的保护作用。ALB促进PGK1降解并诱导Nrf2信号级联激活，用于随后的抗炎和抗氧化损伤。一般来说,ALB在治疗脑缺血中发挥保护作用，并且它可能以PGK1/Nrf2/HO-1信令为目标。因此，ALB可能是减轻脑梗死后神经炎症和保护脑细胞的潜在治疗剂。
