datasheet2_Galectin-3 Mediated Inflammatory Response Contributes to Neurological Recovery by QiShenYiQi in Subacute Stroke Model.zip

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 via 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 via regulating galectin-3 mediated inflammatory reaction.

由于中风复杂的病理表现，有效的治疗手段仍然有限。气神益气（QSYQ），一种能够减轻缺血/再灌注引起的器官损伤的成分型中药，可能为中风治疗及中风后恢复提供一种替代选择。近期，我们报道了QSYQ通过调节神经炎症反应对急性中风具有有益效果。然而，QSYQ在亚急性中风中的作用尚不清楚。本研究中，我们对经过90分钟缺血和8天再灌注的实验性中风大鼠的QSYQ药理作用进行了研究。评估了神经学和运动功能缺陷、脑梗死、脑水肿和血脑屏障（BBB）的完整性。通过基于TMT的定量蛋白质组学技术，对QSYQ治疗后差异表达蛋白进行了鉴定。免疫组化、蛋白质印迹分析、实时荧光定量PCR和ELISA被用于验证蛋白质组学数据，并揭示作用机制。治疗上，连续7天使用QSYQ（600 mg/kg）显著改善了中风大鼠的神经功能恢复，减轻了梗死体积和脑水肿，并缓解了BBB的破坏。生物信息学分析表明，蛋白质岩藻糖-3及其介导的炎症反应与QSYQ的有益效果密切相关。特别是，QSYQ（600 mg/kg）显著下调了CI/RI脑中岩藻糖-3、TNF-α和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，我们的研究结果揭示了QSYQ对CI/RI亚急性期的有效作用部分是通过调节岩藻糖-3介导的炎症反应实现的。