Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China.
J Transl Med. 2024 Oct 17;22(1):946. doi: 10.1186/s12967-024-05735-1.
Intracerebral hemorrhage (ICH) is a severe form of stroke characterized by high incidence and mortality rates. Currently, there is a significant lack of effective treatments aimed at improving clinical outcomes. Our research team has developed a three-dimensional (3D) biological scaffold that incorporates Bergenin, allowing for the sustained release of the compound.
This 3D biological scaffold was fabricated using a combination of photoinitiator, GEMA, silk fibroin, and decellularized brain matrix (dECM) to encapsulate Bergenin through advanced 3D bioprinting techniques. The kinetics of drug release were evaluated through both in vivo and in vitro studies. A cerebral hemorrhage model was established, and a 3D biological scaffold containing Bergenin was transplanted in situ. Levels of inflammatory response, oxidative stress, and apoptosis were quantified. The neurological function of rats with cerebral hemorrhage was assessed on days 1, 3, and 5 using the turning test, forelimb placement test, Longa score, and Bederson score.
The 3D biological scaffold incorporating Bergenin significantly enhances the maintenance of drug concentration in the bloodstream, leading to a marked reduction in inflammatory markers such as IL-6, iNOS, and COX-2 levels in a cerebral hemorrhage model, primarily through the inhibition of the NF-κB pathway. Additionally, the scaffold effectively reduces the expression of hypoxia-inducible factor 1-alpha (HIF-1α) in primary cultured astrocytes, which in turn decreases the production of reactive oxygen species (ROS) and inhibits IL-6 production induced by hemin. Subsequent experiments reveal that the 3D biological scaffold containing Bergenin promotes the activation of the Nrf-2/HO-1 signaling pathway, both in vivo and in vitro, thereby preventing cell death. Moreover, the application of this 3D biological scaffold has been demonstrated to improve drug retention in the bloodstream.
This strategy effectively mitigates inflammation, oxidative stress, and cell death in rats with cerebral hemorrhage by inhibiting the NF-κB pathway while concurrently activating the Nrf-2/HO-1 pathway.
脑出血（ICH）是一种严重的中风形式，具有高发病率和死亡率。目前，针对改善临床结局的有效治疗方法非常缺乏。我们的研究团队开发了一种三维（3D）生物支架，其中包含小檗碱，能够实现该化合物的持续释放。
该 3D 生物支架是通过将光引发剂、GEMA、丝素蛋白和脱细胞脑基质（dECM）结合在一起，使用先进的 3D 生物打印技术来封装小檗碱而制成的。通过体内和体外研究评估了药物释放动力学。建立脑出血模型，并原位移植含有小檗碱的 3D 生物支架。定量检测炎症反应、氧化应激和细胞凋亡水平。使用旋转试验、前肢放置试验、Longa 评分和 Bederson 评分，在脑出血后第 1、3 和 5 天评估大鼠的神经功能。
含小檗碱的 3D 生物支架显著提高了血液中药物浓度的维持，从而在脑出血模型中显著降低了炎症标志物如 IL-6、iNOS 和 COX-2 的水平，主要是通过抑制 NF-κB 通路。此外，该支架还能有效降低原代培养星形胶质细胞中缺氧诱导因子 1-α（HIF-1α）的表达，进而减少活性氧（ROS）的产生，并抑制血红素诱导的 IL-6 产生。随后的实验表明，含小檗碱的 3D 生物支架在体内和体外均能促进 Nrf-2/HO-1 信号通路的激活，从而防止细胞死亡。此外，该 3D 生物支架的应用已被证明可提高血液中药物的保留率。
该策略通过抑制 NF-κB 通路并同时激活 Nrf-2/HO-1 通路，有效减轻脑出血大鼠的炎症、氧化应激和细胞死亡。
