涤痰汤靶向PDE4B减轻卒中后中性粒细胞浸润及神经血管单元损伤  

Targeting PDE4B with Ditan Decoction Inhibits Neutrophil Infiltration to Mitigate Neurovascular Unit Injury

作　　者：俞书红 刘思洁 朱佳怡 范玲 顾佳美 黄昊 罗毅 YU Shuhong;LIU Sijie;ZHU Jiayi;FAN Ling;GU Jiamei;HUANG Hao;LUO Yi(Department of Encephalopathy,Suzhou Integrated Traditional Chinese and Western Medicine Hospital,Suzhou 215101,China;Department of Pharmacy,Suzhou Integrated Traditional Chinese and Western Medicine Hospital,Suzhou 215101,China)

机构地区：[1]苏州市中西医结合医院脑病科,江苏苏州215101 [2]苏州市中西医结合医院药剂科,江苏苏州215101

出　　处：《南京中医药大学学报》2025年第3期306-312,共7页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：吴中区科技计划项目(WZYW2023003);苏州市中西医结合医院科技计划项目(YJ2021002)。

摘　　要：目的探讨涤痰汤(Ditan Decoction,DTD)对缺血性脑卒中的神经保护作用。方法采用小鼠大脑中动脉闭塞(MCAO)模型诱导脑缺血,评估DTD对卒中后NVU损伤的影响。MCAO术后连续3 d每日灌胃给予DTD。通过Transwell中性粒细胞趋化实验探究DTD对中性粒细胞趋化能力的影响。结果在MCAO模型中,DTD治疗显著降低脑梗死体积(P<0.01),并减轻血脑屏障破坏,表现为IgG渗漏减少(P<0.05)和层粘连蛋白表达保留(P<0.05)。此外,DTD抑制中性粒细胞向缺血脑组织的浸润,中性粒细胞弹性蛋白酶(P<0.01)和髓过氧化物酶(P<0.05)水平显著降低。机制上,DTD以剂量依赖性方式抑制中性粒细胞趋化(P<0.01),并下调中性粒细胞迁移关键调控因子磷酸二酯酶4B(PDE4B)的表达(P<0.05)。分子对接分析发现,DTD中的四种活性成分-芹菜素(Apigenin)、牡荆苷(Vitexin)、绿原酸(Chlorogenic acid)和荭草苷(Orientin)与PDE4B具有强结合亲和力(结合能<-5 kcal·mol^(-1)),提示其可能介导DTD的治疗效应。结论涤痰汤通过保护神经血管单元完整性及调控PDE4B依赖性中性粒细胞活性,为缺血性脑卒中提供了一种潜在治疗策略。OBJECTIVE To investigate the neuroprotective effects of Ditan Decoction(DTD)on ischemic stroke.METHODS A mouse middle cerebral artery occlusion(MCAO)model was used to induce cerebral ischemia and assess the role of DTD in post-stroke NVU injury.DTD was gavaged once a day for 3 days after MCAO.Transwell neutrophil chemotaxis assay was used to explore the role of DTD in the neutrophil chemotaxis.RESULTS In the MCAO model,DTD treatment significantly reduced infarct volume(P<0.01)and attenuated blood-brain barrier disruption,as evidenced by decreased IgG leakage and preserved laminin expression(P<0.05).Furthermore,DTD suppressed neutrophil infiltration into ischemic brain tissue,as demonstrated by reduced neutrophil elastase(P<0.01)and myeloperoxidase(P<0.05)levels.Mechanistically,DTD inhibited neutrophil chemotaxis in a dose-dependent manner and downregulated phosphodiesterase 4B(PDE4B),a key regulator of neutrophil migration(P<0.05).Molecular docking analysis identified four active DTD components-apigenin,vitexin,chlorogenic acid,and orientin-with strong binding affinities to PDE4B(binding energies<-5 kcal·mol^(-1)),suggesting their potential role in mediating DTD's therapeutic effects.CONCLUSION These findings highlight DTD as a promising intervention for ischemic stroke,targeting NVU preservation and PDE4B-dependent neutrophil modulation.

关 键 词：涤痰汤 中性粒细胞浸润 缺血性卒中 神经血管单元 PDE4B 髓过氧化物酶 分子对接 

分 类 号：R285.5[医药卫生—中药学]