Xue Dong-Dong, Zhang Xiang, Li De-Wei, Yang Yan-Lan, Liu Jing-Jin
Department of Endocrinology, Shanxi Provincial People's Hospital, Taiyuan 030000, Shanxi Province, China.
Department of Thyroid Surgery, Shanxi Provincial People's Hospital, Taiyuan 030000, Shanxi Province, China.
World J Diabetes. 2023 Feb 15;14(2):110-119. doi: 10.4239/wjd.v14.i2.110.
In recent years, studies have found that the occurrence and development of diabetic cardiomyopathy (DCM) is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1 (PARP-1) activity. PARP-1 activation could be involved in the pathophysiological process of DCM by promoting oxidative stress, the inflammatory response, apoptosis and myocardial fibrosis.
To investigate the mechanism of liraglutide in improving myocardial injury in type 2 diabetic rats, further clarified the protective effect of liraglutide on the heart, and provided a new option for the treatment of DCM.
Forty healthy male SD rats aged 6 wk were randomly divided into two groups, a normal control group ( = 10) and a model group ( = 30), which were fed an ordinary diet and a high-sugar and high-fat diet, respectively. After successful modeling, the rats in the model group were fed a high-glucose and high-fat diet for 4 wk and randomly divided into a model group and an intervention group (further divided into a high-dose group and a low-dose group). The rats were fed a high-glucose and high-fat diet for 8 wk and then started drug intervention. Blood samples were collected from the abdominal aorta to detect fasting blood glucose and lipid profiles. Intact heart tissue was dissected, and its weight was used to calculate the heart weight index. Haematoxylin and eosin staining was used to observe the pathological changes in the myocardium and the expression of PARP-1 in the heart by immunohistochemistry.
The body weight and heart weight index of rats in the model group were significantly increased compared with those in the normal control group, and those in the intervention group were decreased compared with those in the model group, with a more obvious decrease observed in the high-dose group ( < 0.05). In the model group, myocardial fibers were disordered, and inflammatory cells and interstitial fibrosis were observed. The cardiomyopathy of rats in the intervention group was improved to different degrees, the myocardial fibers were arranged neatly, and the myocardial cells were clearly striated; the improvement was more obvious in the high-dose group. Compared with the normal control group, the expression of PARP-1 in myocardial tissue of the model group was increased, and the difference was statistically significant ( < 0.05). After liraglutide intervention, compared with the model group, the expression of PARP-1 in myocardial tissue was decreased, and the reduction was more obvious in the high-dose group ( < 0.05) but still higher than that in the normal control group.
Liraglutide may improve myocardial injury in type 2 diabetic rats by inhibiting the expression of myocardial PARP-1 in a dose-dependent manner.
近年来，研究发现糖尿病性心肌病（DCM）的发生发展与聚腺苷二磷酸核糖聚合酶-1（PARP-1）活性增加密切相关。PARP-1激活可能通过促进氧化应激、炎症反应、细胞凋亡和心肌纤维化参与DCM的病理生理过程。
探讨利拉鲁肽改善2型糖尿病大鼠心肌损伤的机制，进一步明确利拉鲁肽对心脏的保护作用，为DCM的治疗提供新的选择。
将40只6周龄健康雄性SD大鼠随机分为两组，正常对照组（n = 10）和模型组（n = 30），分别给予普通饮食和高糖高脂饮食。造模成功后，模型组大鼠继续给予高糖高脂饮食4周，然后随机分为模型组和干预组（干预组再分为高剂量组和低剂量组）。大鼠继续给予高糖高脂饮食8周后开始药物干预。从腹主动脉采集血样检测空腹血糖和血脂水平。解剖完整的心脏组织，称取心脏重量并计算心脏重量指数。采用苏木精-伊红染色观察心肌病理变化，免疫组织化学法检测心脏中PARP-1的表达。
与正常对照组相比，模型组大鼠体重和心脏重量指数显著增加，与模型组相比，干预组大鼠体重和心脏重量指数降低，高剂量组降低更明显（P < 0.05）。模型组心肌纤维排列紊乱，可见炎性细胞浸润和间质纤维化。干预组大鼠的心肌病得到不同程度改善，心肌纤维排列整齐，心肌细胞横纹清晰；高剂量组改善更明显。与正常对照组相比，模型组心肌组织中PARP-1表达增加，差异有统计学意义（P < 0.05）。利拉鲁肽干预后，与模型组相比，心肌组织中PARP-1表达降低，高剂量组降低更明显（P < 0.05），但仍高于正常对照组。
利拉鲁肽可能通过剂量依赖性抑制心肌PARP-1表达来改善2型糖尿病大鼠心肌损伤。
