Wang Yule, He Shuang, Liu Xinyan, Li Zhixiong, Zhu Lin, Xiao Guangxu, Du Xiaoli, Du Hongxia, Zhang Wen, Zhang Yiqian, Orgah John, Feng Yuxin, Zhang Boli, Zhu Yan
State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin, China.
Front Pharmacol. 2021 Apr 19;12:588587. doi: 10.3389/fphar.2021.588587. eCollection 2021.
Effective therapies for stroke are still limited due to its complex pathological manifestations. QiShenYiQi (QSYQ), a component-based Chinese medicine capable of reducing organ injury caused by ischemia/reperfusion, may offer an alternative option for stroke treatment and post-stroke recovery. Recently, we reported a beneficial effect of QSYQ for acute stroke modulation of the neuroinflammatory response. However, if QSYQ plays a role in subacute stroke remains unknown. The pharmacological action of QSYQ was investigated in experimental stroke rats which underwent 90 min ischemia and 8 days reperfusion in this study. Neurological and locomotive deficits, cerebral infarction, brain edema, and BBB integrity were assessed. TMT-based quantitative proteomics were performed to identify differentially expressed proteins following QSYQ treatment. Immunohistochemistry, western blot analysis, RT-qPCR, and ELISA were used to validate the proteomics data and to reveal the action mechanisms. Therapeutically, treatment with QSYQ (600 mg/kg) for 7 days significantly improved neurological recovery, attenuated infarct volume and brain edema, and alleviated BBB breakdown in the stroke rats. Bioinformatics analysis indicated that protein galectin-3 and its mediated inflammatory response was closely related to the beneficial effect of QSYQ. Specially, QSYQ (600 mg/kg) markedly downregulated the mRNA and protein expression levels of galectin-3, TNF-α, and IL-6 in CI/RI brain as well as serum levels of TNF-α and IL-6. Overall, our findings showed that the effective action of QSYQ against the subacute phase of CI/RI occurs partly regulating galectin-3 mediated inflammatory reaction.
由于中风复杂的病理表现,有效的中风治疗方法仍然有限。芪参益气滴丸(QSYQ)是一种能减少缺血/再灌注引起的器官损伤的中药复方制剂,可能为中风治疗和中风后恢复提供一种替代选择。最近,我们报道了芪参益气滴丸对急性中风神经炎症反应的调节具有有益作用。然而,芪参益气滴丸在亚急性中风中是否发挥作用尚不清楚。本研究在经历90分钟缺血和8天再灌注的实验性中风大鼠中研究了芪参益气滴丸的药理作用。评估了神经和运动功能缺损、脑梗死、脑水肿和血脑屏障完整性。采用基于串联质谱标签(TMT)的定量蛋白质组学方法鉴定芪参益气滴丸治疗后差异表达的蛋白质。采用免疫组织化学、蛋白质免疫印迹分析、逆转录-定量聚合酶链反应(RT-qPCR)和酶联免疫吸附测定(ELISA)来验证蛋白质组学数据并揭示其作用机制。在治疗方面,芪参益气滴丸(600mg/kg)治疗7天可显著改善中风大鼠的神经功能恢复,减小梗死体积和减轻脑水肿,并减轻血脑屏障破坏。生物信息学分析表明,半乳糖凝集素-3蛋白及其介导的炎症反应与芪参益气滴丸的有益作用密切相关。具体而言,芪参益气滴丸(600mg/kg)显著下调了脑缺血/再灌注损伤(CI/RI)模型大鼠脑内半乳糖凝集素-3、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的mRNA和蛋白表达水平以及血清中TNF-α和IL-6的水平。总体而言,我们的研究结果表明,芪参益气滴丸对CI/RI亚急性期的有效作用部分是通过调节半乳糖凝集素-3介导的炎症反应来实现的。