背景:腹主动脉瘤和外周动脉疾病构成重大健康风险,仅次于心脏病和脑中风。手术干预通常涉及临时主动脉钳夹,导致缺血再灌注损伤和组织损伤。秋水仙碱和间充质干细胞已经显示出希望,个别,减轻缺血再灌注损伤,但它们的综合效应仍未得到充分研究。
方法:本研究使用了42只雄性Wistar大鼠,分为六组:对照组,Sham,缺血-再灌注,秋水仙碱,间充质干细胞,和混合(秋水仙碱和间充质干细胞)。缺血再灌注模型包括夹闭腹主动脉60min,然后再灌注120分钟。秋水仙碱和间充质干细胞治疗作为缺血前和缺血后的干预措施,分别。培养间充质干细胞,以流式细胞术为特征,并验证了特定的表面抗原。分析血液和组织样本的氧化应激标志物,一氧化氮代谢物,和使用TUNEL的细胞凋亡。
结果:在血清总抗氧化能力(p<0.001)和炎症标志物(缺血修饰白蛋白,p=0.020)。联合治疗组(Mix)表现出最低的炎症水平。精氨酸水平也显示出显着变化(p=0.028),证实缺血再灌注损伤模型。在肌肉组织中,总抗氧化能力(p=0.022),对称二甲基精氨酸,和瓜氨酸水平(p<0.05)表明一氧化氮代谢。如预期的,在缺血-再灌注损伤组中凋亡显著高。它似乎被秋水仙碱减少了,间充质干细胞,和他们的组合,在混合组中观察到最显著的降低(p<0.001)。
结论:本研究强调了使用秋水仙碱和间充质干细胞联合治疗减轻缺血再灌注损伤引起的肌肉损伤的潜力。需要进一步的研究来了解潜在的机制,并证实这种方法在治疗肢体缺血再灌注损伤中的临床意义。
BACKGROUND: Abdominal aortic aneurysms and peripheral artery disease pose significant health risks, ranking third after heart attacks and cerebral strokes. Surgical interventions often involve temporary aortic clamping, leading to ischemia-reperfusion injury and tissue damage. Colchicine and mesenchymal stem cells have shown promise, individually, in mitigating ischemia-reperfusion injury, but their combined effects remain understudied.
METHODS: This study utilized 42 male Wistar rats, divided into six groups: Control, Sham, Ischemia-Reperfusion, Colchicine, Mesenchymal stem cell, and Mix (colchicine and mesenchymal stem cell). The ischemia-reperfusion model involved clamping the abdominal aorta for 60 min, followed by 120 min of reperfusion. Colchicine and mesenchymal stem cell treatments were administered as pre- and post-ischemia interventions, respectively. Mesenchymal stem cells were cultured, characterized by flow cytometry, and verified for specific surface antigens. Blood and tissue samples were analyzed for oxidative stress markers, nitric oxide metabolites, and apoptosis using TUNEL.
RESULTS: There were significant differences between the groups in terms of the serum total antioxidant capacity (p < 0.001) and inflammation markers (ischemia-modified albumin, p = 0.020). The combined therapy group (Mix) exhibited the lowest inflammation levels. Arginine levels also showed significant variation (p = 0.028), confirming the ischemia-reperfusion injury model. In muscle tissues, the total antioxidant capacity (p = 0.022), symmetric dimethylarginine, and citrulline levels (p < 0.05) indicated nitric oxide metabolism. Apoptosis was notably high in the ischemia-reperfusion injury group as anticipated. It appeared to be reduced by colchicine, mesenchymal stem cells, and their combination, with the most significant decrease observed in the Mix group (p < 0.001).
CONCLUSIONS: This study highlights the potential of using combined colchicine and mesenchymal stem cell therapy to reduce muscle damage caused by ischemia-reperfusion injury. Further research is needed to understand the underlying mechanisms and confirm the clinical significance of this approach in treating extremity ischemia-reperfusion injuries.