白藜芦醇预处理通过下调微小RNA-34a改善糖尿病心肌梗死中高血糖骨髓干细胞移植的心脏恢复能力。

Resveratrol Pretreatment Improved Heart Recovery Ability of Hyperglycemic Bone Marrow Stem Cells Transplantation in Diabetic Myocardial Infarction by Down-Regulating MicroRNA-34a.

作者信息

Zhang Fengyun, Wang Kun, Gao Fei, Xuan Yongli, Liu Xiaohong, Zhang Zhuoqi

机构信息

The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Department of Cardiology, First People's Hospital of Suqian, Suqian, China.

出版信息

Front Pharmacol. 2021 Apr 20;12:632375. doi: 10.3389/fphar.2021.632375. eCollection 2021.

Abstract

To examine the effect of resveratrol (RSV) on bone marrow mesenchymal stem cells (BMSCs) under hyperglycemic conditions and on BMSCs transplantation in diabetic rats with myocardial infarction (MI). , BMSCs were isolated from 3-week-old male Sprague Dawley (SD) rats and cultured under hyperglycemic conditions for up to 28 days. Cell viability was analyzed by cell counting kit-8 (CCK-8) assays. The expression of miR-34a was measured by RT-qPCR. Western blotting was used to examine the protein expression of SIRT1, P21, P16, VEGF and HIF-1α. A senescence-associated β-galactosidase assay was used to examine the senescence level of each group. , a diabetes model was established by feeding rats a high-sugar and high-fat diet for 8 weeks, injecting the animals with streptozotocin (STZ) and continuing high-sugar and high-fat feeding for 4 additional weeks. Then, left anterior descending coronary artery (LAD) cessation was used to established the myocardial infarction (MI) models. Each group of rats was transplanted with differentially preconditioned BMSCs after myocardial infarction. Ultrasound was used to analyze cardiac function 1 and 3 weeks after the operation, and frozen heart sections were used for immunohistochemical analysis, Masson staining and CD31 measurement. In addition, ELISA analysis of serum cytokine levels was performed. This study showed that the viability of BMSCs cultured under hyperglycemic conditions was decreased, the cells became senescent. Besides, an obviously increased in the expression of miR-34a was detected. Moreover, RSV preconditioning reduced the expression of miR-34a in BMSCs after high glucose stimulation and rejuvenated BMSCs under hyperglycemic conditions. Further analysis showed that the transplantation of RSV-BMSCs were benefit to heart recovery following infarction in diabetic rats, promoted proangiogenic factor release and increased arteriole and capillary densities. RSV rejuvenated BMSCs after chronic hyperglycemia-induced senescence by interacting with miR-34a and optimized the therapeutic effect of BMSCs on diabetes with myocardial infarction.

摘要

研究白藜芦醇(RSV)在高糖条件下对骨髓间充质干细胞(BMSCs)的影响以及对糖尿病心肌梗死(MI)大鼠BMSCs移植的影响。从3周龄雄性Sprague Dawley(SD)大鼠中分离BMSCs,并在高糖条件下培养长达28天。通过细胞计数试剂盒-8(CCK-8)测定分析细胞活力。通过RT-qPCR测量miR-34a的表达。使用蛋白质印迹法检测SIRT1、P21、P16、VEGF和HIF-1α的蛋白表达。使用衰老相关β-半乳糖苷酶测定法检测每组的衰老水平。通过给大鼠喂食高糖高脂饮食8周,注射链脲佐菌素(STZ)并继续高糖高脂喂养4周来建立糖尿病模型。然后,使用左冠状动脉前降支结扎来建立心肌梗死(MI)模型。每组大鼠在心肌梗死后移植经过不同预处理的BMSCs。术后1周和3周使用超声分析心脏功能,并使用冷冻心脏切片进行免疫组织化学分析、Masson染色和CD31测量。此外,进行血清细胞因子水平的ELISA分析。本研究表明,在高糖条件下培养的BMSCs活力降低,细胞衰老。此外,检测到miR-34a的表达明显增加。此外,RSV预处理降低了高糖刺激后BMSCs中miR-34a的表达,并使高糖条件下的BMSCs恢复活力。进一步分析表明,RSV-BMSCs移植有利于糖尿病大鼠心肌梗死后的心脏恢复,促进促血管生成因子释放并增加小动脉和毛细血管密度。RSV通过与miR-34a相互作用使慢性高血糖诱导衰老后的BMSCs恢复活力,并优化了BMSCs对糖尿病合并心肌梗死的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b73e/8223511/d45f95170e16/fphar-12-632375-g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索