College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Tissue Cell. 2024 Oct;90:102515. doi: 10.1016/j.tice.2024.102515. Epub 2024 Aug 5.
With the development of Type 1 diabetes mellitus (T1DM), various complications can be caused. Hyperglycemia affects the microenvironment of cardiomyocytes, changes endoplasmic reticulum homeostasis, triggers unfolding protein response and eventually promotes myocardial apoptosis. However, insulin therapy alone cannot effectively combat the complications caused by T1DM. Forty adult beagles were randomly divided into five groups: control group, diabetes mellitus group, insulin group, insulin combined with NAC group, and NAC group. 24-hour blood glucose, 120-day blood glucose, 120-day body weight, and serum FMN content were observed, furthermore, hematoxylin-eosin staining, Periodic acid Schiff reagent staining, and Sirius red staining of the myocardium were evaluated. The protein expressions of GRP78, ATF6, IRE1, PERK, JNK, CHOP, caspase 3, Bcl2, and Bax were detected. Results of the pathological section of myocardial tissue indicated that insulin combined with NAC therapy could improve myocardial pathological injury and glycogen deposition. Additionally, insulin combined with NAC therapy down-regulates the expression of GRP78, ATF6, IRE1, PERK, JNK, CHOP, caspase3, and Bax. These findings suggest that NAC has a phylactic effect on myocardial injury in beagles with T1DM, and the mechanism may be related to the improvement of endoplasmic reticulum stress-induced apoptosis.
随着 1 型糖尿病（T1DM）的发展，可能会引起各种并发症。高血糖会影响心肌细胞的微环境，改变内质网的稳态，触发未折叠蛋白反应，最终促进心肌细胞凋亡。然而，单独使用胰岛素治疗并不能有效对抗 T1DM 引起的并发症。将 40 只成年比格犬随机分为 5 组：对照组、糖尿病组、胰岛素组、胰岛素联合 NAC 组、NAC 组。观察 24 小时血糖、120 天血糖、120 天体重和血清 FMN 含量，同时评估心肌苏木精-伊红染色、过碘酸希夫试剂染色和天狼猩红染色。检测 GRP78、ATF6、IRE1、PERK、JNK、CHOP、caspase3、Bcl2 和 Bax 的蛋白表达。心肌组织病理切片结果表明，胰岛素联合 NAC 治疗可改善心肌病理损伤和糖原沉积。此外，胰岛素联合 NAC 治疗可下调 GRP78、ATF6、IRE1、PERK、JNK、CHOP、caspase3 和 Bax 的表达。这些发现表明，NAC 对 T1DM 比格犬的心肌损伤具有预防作用，其机制可能与改善内质网应激诱导的细胞凋亡有关。
