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秋水仙碱分散体与骨髓间充质干细胞疗法对大鼠主动脉缺血再灌注模型骨骼肌损伤的影响

The Effects of Colchicum Dispert and Bone Marrow-Derived Mesenchymal Stem Cell Therapy on Skeletal Muscle Injury in a Rat Aortic Ischemia-Reperfusion Model.

作者信息

Orhan Atilla, Çiçek Ömer Faruk, Öztürk Bahadır, Akbayrak Hakan, Ünlükal Nejat, Vatansev Hakan, Solmaz Merve, Büyükateş Mustafa, Aniç Seda, Ovalı Fadime, Almaghrebi Eissa, Akat Fatma, Vatansev Hüsamettin

机构信息

Department of Cardiovascular Surgery, Medical Faculty, Selçuk University, Konya 42250, Turkey.

Department of Biochemistry, Medical Faculty, Selçuk University, Konya 42250, Turkey.

出版信息

J Cardiovasc Dev Dis. 2024 Aug 16;11(8):251. doi: 10.3390/jcdd11080251.

Abstract

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 ( < 0.001) and inflammation markers (ischemia-modified albumin, = 0.020). The combined therapy group (Mix) exhibited the lowest inflammation levels. Arginine levels also showed significant variation ( = 0.028), confirming the ischemia-reperfusion injury model. In muscle tissues, the total antioxidant capacity ( = 0.022), symmetric dimethylarginine, and citrulline levels ( < 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 ( < 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.

摘要

背景

腹主动脉瘤和外周动脉疾病构成重大健康风险,在心脏病发作和中风之后位列第三。手术干预通常涉及临时主动脉夹闭,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各自在减轻缺血再灌注损伤方面已显示出前景,但它们的联合效果仍未得到充分研究。

方法

本研究使用42只雄性Wistar大鼠,分为六组:对照组、假手术组、缺血再灌注组、秋水仙碱组、间充质干细胞组和联合组(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60分钟,随后再灌注120分钟。秋水仙碱和间充质干细胞治疗分别作为缺血前和缺血后干预措施。培养间充质干细胞,通过流式细胞术进行表征,并验证其特异性表面抗原。使用TUNEL分析血液和组织样本中的氧化应激标志物、一氧化氮代谢产物和细胞凋亡情况。

结果

各组之间在血清总抗氧化能力(<0.001)和炎症标志物(缺血修饰白蛋白,=0.020)方面存在显著差异。联合治疗组(联合组)表现出最低的炎症水平。精氨酸水平也显示出显著差异(=0.028),证实了缺血再灌注损伤模型。在肌肉组织中,总抗氧化能力(=0.022)、对称二甲基精氨酸和瓜氨酸水平(<0.05)表明存在一氧化氮代谢。正如预期的那样,缺血再灌注损伤组的细胞凋亡明显较高。秋水仙碱、间充质干细胞及其组合似乎可使其减少,联合组减少最为显著(<0.001)。

结论

本研究突出了使用秋水仙碱和间充质干细胞联合疗法减少缺血再灌注损伤所致肌肉损伤的潜力。需要进一步研究以了解其潜在机制,并证实该方法在治疗肢体缺血再灌注损伤中的临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c289/11354812/e47b2d26bb1b/jcdd-11-00251-g001.jpg

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