State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China; Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, 220 Dongting Road, TEDA, Tianjin 300457, China.
State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin Tasly Holding Group Co., Ltd., Tianjin, China.
Biomed Pharmacother. 2020 May;125:109945. doi: 10.1016/j.biopha.2020.109945. Epub 2020 Feb 3.
Cerebral ischemia/reperfusion injury (CI/RI) is a common feature of ischemic stroke, involving a period of impaired blood supply to the brain, followed by the restoration of cerebral perfusion through medical intervention. Although ischemia and reperfusion brain damage is a complex pathological process with an unclear physiological mechanism, more attention is currently focused on the neuroinflammatory response of an ischemia/reperfusion origin, and anti-inflammatory appears to be a potential therapeutic strategy following ischemic stroke. QiShenYiQi (QSYQ), a component-based Chinese medicine with Qi-tonifying and blood-activating property, has pharmacological actions of anti-inflammatory, antioxidant, mitochondrial protectant, anti-apoptosis, and antiplatelet aggregation. We have previously reported that the cardioprotective effect of QSYQ against ischemia/reperfusion injury is via improvement of mitochondrial functional integrity. In this research work, we aimed to investigate the possible mechanism involved in the neuroprotection of QSYQ in mice model of cerebral ischemia/reperfusion injury based on the inflammatory pathway. The cerebral protection was evaluated in the stroke mice after 24 h reperfusion by assessing the neurological deficit, cerebral infarction, brain edema, BBB functionality, and via histopathological assessment. TCM-based network pharmacology method was performed to establish and analyze compound-target-disease & function-pathway network so as to find the possible mechanism linking to the role of QSYQ in CI/RI. In addition, RT-qPCR was used to verify the accuracy of predicted signaling gene expression. As a result, improvement of neurological outcome, reduction of infarct volume and brain edema, a decrease in BBB disruption, and amelioration of histopathological alteration were observed in mice pretreated with QSYQ after experimental stroke surgery. Network pharmacology analysis revealed neuroinflammatory response was associated with the action of QSYQ in CI/RI. RT-qPCR data showed that the mice pretreated with QSYQ could significantly decrease IFNG-γ, IL-6, TNF-α, NF-κB p65, and TLR-4 mRNA levels and increase TGF-β1 mRNA level in the brain compared to the untreated mice after CI/RI (p < 0.05). In conclusion, our study indicated the cerebral protective effect of pretreatment with QSYQ against CI/RI, which may be partly related to its potential to the reduction of neuroinflammatory response in a stroke subject.
脑缺血/再灌注损伤（CI/RI）是缺血性中风的一个共同特征，涉及脑血流供应受损的一段时间，随后通过医疗干预恢复脑灌注。尽管缺血和再灌注脑损伤是一个复杂的病理过程，其生理机制尚不清楚，但目前更多地关注缺血/再灌注来源的神经炎症反应，抗炎似乎是缺血性中风后的一种潜在治疗策略。芪参益气（QSYQ）是一种具有补气活血作用的基于成分的中药，具有抗炎、抗氧化、线粒体保护、抗细胞凋亡和抗血小板聚集的药理作用。我们之前报道过，QSYQ 对缺血/再灌注损伤的心脏保护作用是通过改善线粒体功能的完整性来实现的。在这项研究工作中，我们旨在基于炎症途径，研究 QSYQ 在脑缺血/再灌注损伤小鼠模型中神经保护作用的可能机制。通过评估神经功能缺损、脑梗死、脑水肿、BBB 功能和组织病理学评估，在 24 小时再灌注后评估中风小鼠的脑保护作用。采用基于中医的网络药理学方法建立和分析化合物-靶标-疾病和功能-途径网络，以找到与 QSYQ 在 CI/RI 中的作用相关的可能机制。此外，还使用 RT-qPCR 来验证预测信号基因表达的准确性。结果显示，在实验性中风手术后，用 QSYQ 预处理的小鼠的神经功能改善、梗死体积和脑水肿减少、BBB 破坏减少以及组织病理学改变改善。网络药理学分析显示，神经炎症反应与 QSYQ 在 CI/RI 中的作用有关。RT-qPCR 数据显示，与未经处理的小鼠相比，用 QSYQ 预处理的小鼠在 CI/RI 后大脑中 IFNG-γ、IL-6、TNF-α、NF-κB p65 和 TLR-4 mRNA 水平显著降低，TGF-β1 mRNA 水平升高（p<0.05）。总之，我们的研究表明，QSYQ 预处理对 CI/RI 具有脑保护作用，这可能与其在中风患者中降低神经炎症反应的潜力有关。
