随着1型糖尿病(T1DM)的发展,可引起各种并发症。高血糖影响心肌细胞的微环境,改变内质网稳态,触发解折叠蛋白反应并最终促进心肌细胞凋亡。然而,单纯胰岛素治疗不能有效对抗T1DM引起的并发症。将40只成年小猎犬随机分为5组:对照组,糖尿病组,胰岛素组,胰岛素联合NAC组,NAC集团。24小时血糖,120天血糖,120天体重,并观察血清FMN含量,此外,苏木精-伊红染色,周期性酸性希夫试剂染色,评价心肌的天狼星红染色。GRP78、ATF6、IRE1、PERK、JNK,CHOP,检测caspase3、Bcl2和Bax。心肌组织病理切片结果显示,胰岛素联合NAC治疗可改善心肌组织病理损伤和糖原沉积。此外,胰岛素联合NAC治疗下调GRP78、ATF6、IRE1、PERK、JNK,CHOP,caspase3和Bax.这些发现表明,NAC对T1DM比格犬的心肌损伤具有保护作用,其机制可能与改善内质网应激诱导的细胞凋亡有关。
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.