葡萄糖波动通过增强 Txnip 和 Akt 的相互作用加重心肌细胞凋亡。

Glucose fluctuations aggravate cardiomyocyte apoptosis by enhancing the interaction between Txnip and Akt.

机构信息

Department of Cardiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, China.

Wuxi School of Medicine, Jiangnan University, Wuxi, 214023, China.

出版信息

BMC Cardiovasc Disord. 2024 Sep 3;24(1):470. doi: 10.1186/s12872-024-04134-0.

DOI:10.1186/s12872-024-04134-0

PMID:39223509

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11370038/

Abstract

BACKGROUND

Glucose fluctuations may be involved in the pathophysiological process of cardiomyocyte apoptosis, but the exact mechanism remains elusive. This study focused on exploring the mechanisms related to glucose fluctuation-induced cardiomyocyte apoptosis.

METHODS

Diabetic rats established via an injection of streptozotocin were randomized to five groups: the controlled diabetic (CD) group, the uncontrolled diabetic (UD) group, the glucose fluctuated diabetic (GFD) group, the GFD group rats with the injection of 0.9% sodium chloride (NaCl) (GFD + NaCl) and the GFD group rats with the injection of N-acetyl-L-cysteine (NAC) (GFD + NAC). Twelve weeks later, cardiac function and apoptosis related protein expressions were tested. Proteomic analysis was performed to further analyze the differential protein expression pattern of CD and GFD.

RESULTS

The left ventricular ejection fraction levels and fractional shortening levels were decreased in the GFD group, compared with those in the CD and UD groups. Positive cells tested by DAB-TUNEL were increased in the GFD group, compared with those in the CD group. The expression of Bcl-2 was decreased, but the expressions of Bax, cleaved caspase-3 and cleaved caspase-9 were increased in response to glucose fluctuations. Compared with CD, there were 527 upregulated and 152 downregulated proteins in GFD group. Txnip was one of the differentially expressed proteins related to oxidative stress response. The Txnip expression was increased in the GFD group, while the Akt phosphorylation level was decreased. The interaction between Txnip and Akt was enhanced when blood glucose fluctuated. Moreover, the application of NAC partially reversed glucose fluctuations-induced cardiomyocyte apoptosis.

CONCLUSIONS

Glucose fluctuations lead to cardiomyocyte apoptosis by up-regulating Txnip expression and enhancing Txnip-Akt interaction.

摘要

背景

血糖波动可能参与了心肌细胞凋亡的病理生理过程，但具体机制仍不清楚。本研究旨在探讨与葡萄糖波动诱导的心肌细胞凋亡相关的机制。

方法

通过链脲佐菌素注射建立糖尿病大鼠模型，随机分为五组：对照糖尿病（CD）组、未控制糖尿病（UD）组、葡萄糖波动糖尿病（GFD）组、GFD 组大鼠注射 0.9%氯化钠（GFD+NaCl）和 GFD 组大鼠注射 N-乙酰-L-半胱氨酸（GFD+NAC）。12 周后，检测心功能和凋亡相关蛋白表达。进行蛋白质组学分析以进一步分析 CD 和 GFD 的差异蛋白表达模式。

结果

与 CD 和 UD 组相比，GFD 组左心室射血分数和短轴缩短率降低。GFD 组 DAB-TUNEL 阳性细胞增多。Bcl-2 表达减少，而 Bax、cleaved caspase-3 和 cleaved caspase-9 的表达增加。与 CD 组相比，GFD 组有 527 个上调蛋白和 152 个下调蛋白。Txnip 是与氧化应激反应相关的差异表达蛋白之一。GFD 组 Txnip 表达增加，而 Akt 磷酸化水平降低。当血糖波动时，Txnip 和 Akt 之间的相互作用增强。此外，NAC 的应用部分逆转了葡萄糖波动诱导的心肌细胞凋亡。