■志龙活血通瘀(ZL)胶囊是一种经典的中药(TCM),疗效满意。内皮细胞(EC)功能障碍在心肌纤维化(MF)中起重要作用。但在MF的发展过程中,ZL胶囊对EC功能障碍的治疗作用尚不清楚。本研究旨在探讨ZL胶囊对MF体内EC功能障碍的影响。
■通过注射异丙肾上腺素14天在体内建立MF模型,同时,我们在体内检测了ZL胶囊对MF的治疗作用。一种结合生物标志物检查的综合方法,超声心动图和心肌纤维化状况使用苏木精-伊红染色,Masson染色,进行天狼星红染色以评估ZL胶囊对MF的功效。随后,进行综合免疫荧光染色以评价ZL胶囊对EC功能障碍的治疗效果。
■在实验之前,对已发表的单细胞测序数据进行分析,发现EC功能障碍起着重要作用.进一步的药理结果表明,ZL胶囊可以减轻纤维化损伤和胶原纤维沉积。机制研究结果表明,EC中内皮-间质转化(EndMT)和MHC-II类(MHC-II)的表达得到改善。此外,ZL胶囊可以通过干预EC介导的CD4T细胞的活化来减轻MF过程中的炎症反应。第一次,我们提供的证据表明,ZL胶囊可以通过调节EndMT和MHC-II的表达来减轻EC功能障碍,从而改善MF。
■心肌纤维化,中草药,传统医学,内皮,功能障碍,内皮-间质转化。
UNASSIGNED: Zhilong Huoxue Tongyu (ZL) capsule is a classical traditional Chinese medicine (TCM) with satisfactory curative effects. Endothelial cell (EC) dysfunction plays an important role during myocardial fibrosis (MF). But the therapeutic effect of ZL capsule on EC dysfunction remains unknown in the development of MF. This study aims to investigate the effect of ZL capsule on EC dysfunction during MF in vivo.
UNASSIGNED: The model of MF is established in vivo by injecting isoproterenol for 14 days, simultaneously, we examined the therapeutic effect of ZL capsule on MF in vivo. An integrative approach combining biomarker examination, echocardiography and myocardial fibrosis condition using Hematoxylin-eosin staining, Masson staining, and Sirius red staining were performed to assess the efficacy of ZL capsule against MF. Subsequently, comprehensive immunofluorescence staining was performed to evaluate the therapeutic effect of ZL capsule on EC dysfunction.
UNASSIGNED: Prior to experiments, analysis of the published single-cell sequencing data was performed and it was discovered that EC dysfunction plays an important role. Further pharmacological results showed that ZL capsule could alleviate fibrosis injury and collagen fiber deposition. The mechanism investigation results showed that the endothelial-to-mesenchymal transition (EndMT) and
MHC class-II (
MHC-II) expression in EC were improved. In addition, ZL capsule can attenuate the inflammatory response during MF by intervening the activation of CD4+T cell mediated by EC. For the first time, we provided evidence that ZL capsule could improve MF by alleviating EC dysfunction via the regulation of EndMT and expression of
MHC-II.
UNASSIGNED: Myocardial fibrosis, Chinese Herbal Medicine, Traditional Medicine, Endothelium, dysfunction, Endothelial-to-mesenchymal transition.