基于DLL4/Notch1通路的加味血府逐瘀汤干预MIRI大鼠血管新生机制探讨  

Exploring the mechanism of angiogenesis in MIRI rats through the Modified Xuefu Zhuyu Decoction based on the DLL4/Notch1 signaling pathway

作　　者：乔鹏 刘岩松 刘婷[1] 张剑航 肖佳璇 潘单依 刘旺华[1,2,3] QIAO Peng;LIU Yan-song;LIU Ting;ZHANG Jian-hang;XIAO Jia-xuan;PAN Dan-yi;LIU Wang-hua(Provincial Key Laboratory of TCM Diagnostics,Hunan University of Chinese Medicine,Changsha 410208,China;Hunan Engineering Technology Research Center For Medicinal and Functional Food,Hunan University of Chinese Medicine,Changsha 410208,China;Key Laboratory of TCM Heart and Lung Syndrome Differentiation&Medicated Diet and Dietotherapy,Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学中医诊断学湖南省重点实验室,湖南长沙410208 [2]湖南中医药大学药食同源功能性食品工程技术研究中心,湖南长沙410208 [3]湖南中医药大学中医心肺病证辨证与药膳食疗重点研究室,湖南长沙410208

出　　处：《时珍国医国药》2025年第2期201-208,共8页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(81473567);湖南省自然科学基金(2023JJ30451);湖南省中医药科研计划重点项目(2021013,A2023038);湖南省教育厅科学研究项目重点项目(23A0308)。

摘　　要：目的基于DLL4/Notch1通路探讨加味血府逐瘀汤对心肌缺血再灌注损伤(MIRI)后大鼠血管新生的影响。方法将60只SPF级大鼠随机分为假手术组、模型组、丹参酮组、加味血府逐瘀汤组(简称中药组)和加味血府逐瘀汤+通路抑制剂(DAPT)组(简称中药+DAPT组)。采用冷刺激结合注射阿霉素法构建心阳虚血瘀证模型,证候造模6周后进行手术造模。采用超声心动图检测大鼠心功能,血流变仪检测血液流变性,HE染色法观察病理形态,免疫组化法检测微血管密度,Western blot法检测DLL4、Notch1、VEGF、bFGF蛋白表达。结果与假手术组相比,模型组阳虚体征评分升高,肛温、EF值降低,低、中、高切值显著升高,MVD值升高,VEGF、bFGF、DLL4、Notch1蛋白表达升高(P<0.01,P<0.05);与模型组相比,中药组阳虚体征评分、EF值降低,肛温升高,低、中、高切值下降,MVD值升高,VEGF、bFGF、Dll4、Notch1蛋白表达升高(P<0.01,P<0.05)。结论加味血府逐瘀汤能改善MIRI大鼠阳虚血瘀状态,增加心肌微血管密度,其机制可能与上调VEGF、bFGF、DLL4、Notch1的表达有关。Objective Sixty SPF-grade rats were randomly divided into a sham group,a model group,a tanshinone group,a MXZD group(referred to as the Chinese medicinal or briefly CM group),and a MXZD+pathway inhibitor(DAPT)group(referred to as the CM+DAPT group).A model of heart yang deficiency with blood stasis syndrome was established through a combination of cold stimulation and adriamycin injection.After 6 weeks of syndrome modeling,surgery was performed,and the rats'macroscopic signs(yang deficiency scores)were evaluated using a syndrome scoring scale.Echocardiography was used to assess cardiac function,a rheometer to measure blood viscosity,HE staining to observe histopathological morphology,immunohistochemistry to detect microvascular density,and Western blot(WB)to detect the expression of DLL4,Notch1,VEGF,and bFGF proteins.Results Compared with the sham group,the yang deficiency scores in the model group increased,the anal temperature and EF value decreased,the low,medium and high cut values significantly increased,the MVD value increased,and the expression of VEGF,bFGF,Dll4 and Notch1 protein increased(P<0.01,P<0.05);compared with the model group,the yang deficiency scores and EF value in the CM group decreased,the anal temperature increased,the low,medium and high cut-off values decreased,the MVD value increased,and the expression of VEGF,bFGF,Dll4 and Notch1 protein increased(P<0.01,P<0.05).Conclusion MXZD can relieve yang deficiency and blood stasis and increase myocardial microvessel density in rats with MIRI,and its mechanism may be related to the up-regulated expression of VEGF,bFGF,Dll4 and Notch1 proteins.

关 键 词：血府逐瘀汤 NOTCH通路 血管新生 阳虚血瘀证 心肌缺血再灌注损伤 

分 类 号：R285.5[医药卫生—中药学]