脊髓损伤(SCI)是中枢神经系统常见且严重的损伤,造成严重后果。这种损伤的特点是运动,感官,和受影响的脊柱节段以下的排泄功能障碍。骨髓间充质干细胞(BMSCs)的移植已成为SCI的潜在治疗方法。然而,BMSCs在脊髓微环境中的低存活率和分化率显着限制了其治疗效率。牛磺熊去氧胆酸(TUDCA),在熊胆中发现的一种活性成分,已经证明了它的神经保护作用,抗氧化剂,和对SCI的抗凋亡作用。因此,本研究旨在研究使用SCI动物模型联合TUDCA和BMSC移植的可能益处.结果表明,TUDCA显着增强BMSC的活力并减少细胞凋亡(通过膜联蛋白V-FITC评估,TUNEL,Bax,Bcl-2和Caspase-3)以及氧化应激(通过ROS评估,GSH,SOD,和MDA)在体外和体内。此外,TUDCA加速组织再生(通过HE评估,Nissl,MAP2,MBP,在SCI中BMSC移植后,TUJ1和GFAP)和改善的功能恢复(通过BBB评分评估)。这些作用是通过Nrf-2信号通路介导的,如Nrf-2、NQO-1和HO-1表达水平的上调所证明的。总的来说,这些结果表明,TUDCA可作为BMSC移植治疗SCI的有价值的辅助手段,有可能增强其治疗效果.
Spinal cord injury (SCI) is a prevalent and significant injury to the central nervous system, resulting in severe consequences. This injury is characterized by motor, sensory, and excretory dysfunctions below the affected spinal segment. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has emerged as a potential treatment for SCI. However, the low survival as well as the differentiation rates of BMSCs within the spinal cord microenvironment significantly limit their therapeutic efficiency. Tauroursodeoxycholic acid (
TUDCA), an active ingredient found in bear bile, has demonstrated its neuroprotective, antioxidant, and antiapoptotic effects on SCI. Thus, the present study was aimed to study the possible benefits of combining
TUDCA with BMSC transplantation using an animal model of SCI. The results showed that
TUDCA significantly enhanced BMSC viability and reduced apoptosis (assessed by Annexin V-FITC, TUNEL, Bax, Bcl-2, and Caspase-3) as well as oxidative stress (assessed by ROS, GSH, SOD, and MDA) both in vitro and in vivo. Additionally,
TUDCA accelerated tissue regeneration (assessed by HE, Nissl, MAP2, MBP, TUJ1, and GFAP) and improved functional recovery (assessed by BBB score) following BMSC transplantation in SCI. These effects were mediated via the Nrf-2 signaling pathway, as evidenced by the upregulation of Nrf-2, NQO-1, and HO-1 expression levels. Overall, these results indicate that
TUDCA could serve as a valuable adjunct to BMSC transplantation therapy for SCI, potentially enhancing its therapeutic efficacy.