Diabetic cardiomyopathy is known to involve two forms of cardiac cell death: apoptosis and necrosis. However, it remains unknown whether hyperglycemia-induced apoptosis in the H9c2 cell culture system is inhibited by parasympathetic ganglionic neurons (PGN) derived exosomes (exos). We isolated PGN and sympathetic ganglionic neurons (SGN) from the right stellate ganglion in rats, and derived exos from these sources. H9c2 cells were divided into 4 groups: (1) Control, (2) H9c2 + Glucose (100 mmol/L), (3) H9c2 + Glucose + PGN-exos, and (4) H9c2 + Glucose + SGN-exos. We determined cell proliferation and viability with an MTT assay kit, and assessed apoptotic cell death with TUNEL staining and ELISA. Data were further confirmed by analyzing the presence of pro-apoptotic proteins Caspase-3 and Bax, and anti-apoptotic protein Bcl-2. Glucose exposed H9c2 cells significantly reduced cell viability, which was improved by PGN-exos, but not by SGN-exos. Furthermore, increased apoptosis in hyperglycemia in H9c2 cells was confirmed with TUNEL staining and cell death ELISA which demonstrated significantly (p < 0.05) reduction with PGN-exos treatment, but not with SGN-exos. Moreover, high expression of pro-apoptotic proteins Caspase-3 and Bax was reduced following treatment with PGN-exos; however, SGN-exos were unable to reduce the expression. Significantly reduced anti-apoptotic protein Bcl-2 following glucose treatment was improved with PGN-exos. Therefore, our data suggest that hyperglycemia induces apoptosis in H9c2 cells and decreases cell viability, and that PGN-exos are able to inhibit apoptosis, improve cell viability, and restore levels of anti-apoptotic protein Bcl-2.

中文翻译：

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源自心脏副交感神经节神经元的外泌体抑制高血糖心肌细胞凋亡。

已知糖尿病性心肌病涉及两种形式的心脏细胞死亡：细胞凋亡和坏死。然而，尚不清楚 H9c2 细胞培养系统中高血糖诱导的细胞凋亡是否被副交感神经节神经元 (PGN) 衍生的外泌体 (exos) 抑制。我们从大鼠的右星状神经节中分离出 PGN 和交感神经节神经元 (SGN)，并从这些来源获得外显子。H9c2 细胞分为 4 组：(1) 对照，(2) H9c2 + 葡萄糖 (100 mmol/L)，(3) H9c2 + 葡萄糖 + PGN-exos，和 (4) H9c2 + 葡萄糖 + SGN-exos。我们用 MTT 检测试剂盒测定细胞增殖和活力，并用 TUNEL 染色和 ELISA 评估凋亡细胞死亡。通过分析促凋亡蛋白 Caspase-3 和 Bax 以及抗凋亡蛋白 Bcl-2 的存在进一步证实了数据。葡萄糖暴露的 H9c2 细胞显着降低了细胞活力，PGN-exos 改善了这种情况，但 SGN-exos 没有改善。此外，用 TUNEL 染色和细胞死亡 ELISA 证实了 H9c2 细胞中高血糖的细胞凋亡增加，这表明 PGN-exos 治疗显着（p < 0.05）减少，但 SGN-exos 没有。此外，PGN-exos 处理后促凋亡蛋白 Caspase-3 和 Bax 的高表达降低；然而，SGN-exos 无法降低表达。PGN-exos 改善了葡萄糖处理后显着降低的抗凋亡蛋白 Bcl-2。因此，我们的数据表明高血糖会诱导 H9c2 细胞凋亡并降低细胞活力，而 PGN-exos 能够抑制细胞凋亡、提高细胞活力并恢复抗凋亡蛋白 Bcl-2 的水平。