The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China.
The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China; Hunan Academy of Chinese Medicine, Changsha 410006, China.
Phytomedicine. 2024 Jul;129:155609. doi: 10.1016/j.phymed.2024.155609. Epub 2024 Apr 8.
Angiogenesis is an effective method for promoting neurological function recovery after cerebral ischemia (CI). Buyang Huanwu decoction (BHD) is a traditional Chinese medicinal recipe that is frequently employed for CI treatment. Previous investigations have validated that it promotes angiogenesis following CI. Nevertheless, the precise mechanism by which it does this has yet to be completely understood.
This study aims to examine the underlying mechanism through which BHD facilitates angiogenesis following CI by regulating the exosomal MALAT1/YAP1/HIF-1α signaling axis, specifically via the involvement of caveolin-1 (Cav1), an endocytosis-associated protein.
A CI model was created using middle cerebral artery occlusion (MCAO). Following the administration of multiple doses of BHD, various parameters, including the neurobehavioral score, pathological damage, and angiogenesis, were assessed in each group of mice to identify the optimal dosage of BHD for treating CI. The molecular processes underlying the angiogenic implications of BHD following CI were investigated exhaustively by employing single-cell sequencing. Finally, the involvement of Cav1 was confirmed in Cav1 knockout mice and Cav1-silenced stably transfected strains to validate the mechanism by which BHD increases angiogenesis following CI.
BHD could promote angiogenesis after CI. Single-cell sequencing results suggested that its potential mechanism of action might be connected with Cav1 and the exosomal MALAT1/YAP1/HIF-1α signaling axis. BHD could promote angiogenesis after CI by regulating the exosomal MALAT1/YAP1/HIF-1α axis through Cav1, as validated in vivo and in vitro experiments. Accordingly, Cav1 may be a key target of BHD in promoting angiogenesis after CI.
This investigation represents the initial attempt to comprehensively ascertain the underlying mechanism of action of BHD in treating CI using single-cell sequencing, gene-knockout mice, and stable transfected cell lines, potentially associated with the modulation of the exosomal MALAT1/YAP1/HIF-1α axis by Cav1. Our findings offer novel empirical evidence for unraveling the regulatory pathways through which Cav1 participates in angiogenesis following CI and shed light on the potential mechanisms of BHD.
血管生成是促进脑缺血（CI）后神经功能恢复的有效方法。补阳还五汤（BHD）是一种常用于治疗 CI 的中药方剂，已被证实可促进 CI 后的血管生成。然而，其具体作用机制尚未完全阐明。
本研究旨在通过调节外泌体 MALAT1/YAP1/HIF-1α 信号轴来探讨 BHD 通过 Cav1（一种内吞相关蛋白）促进 CI 后血管生成的潜在机制。
采用大脑中动脉闭塞（MCAO）建立 CI 模型。在给予多次 BHD 给药后，通过评估各组小鼠的神经行为评分、病理损伤和血管生成等参数，确定治疗 CI 的 BHD 最佳剂量。通过单细胞测序全面研究 BHD 对 CI 后血管生成的影响所涉及的分子过程。最后，通过 Cav1 敲除小鼠和 Cav1 沉默稳定转染株证实 Cav1 在 BHD 促进 CI 后血管生成中的作用，验证 BHD 增加 CI 后血管生成的机制。
BHD 可促进 CI 后血管生成。单细胞测序结果表明，其作用机制可能与 Cav1 和外泌体 MALAT1/YAP1/HIF-1α 信号轴有关。BHD 可通过 Cav1 调节外泌体 MALAT1/YAP1/HIF-1α 轴促进 CI 后血管生成，体内和体外实验均得到验证。因此，Cav1 可能是 BHD 促进 CI 后血管生成的关键靶点。
本研究首次采用单细胞测序、基因敲除小鼠和稳定转染细胞系全面探讨了 BHD 治疗 CI 的作用机制，可能与 Cav1 调节外泌体 MALAT1/YAP1/HIF-1α 轴有关。本研究为 Cav1 参与 CI 后血管生成的调控机制提供了新的实验依据，也为 BHD 的作用机制提供了新的见解。
