Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Feb 15, 2023; 14(2): 110-119
Published online Feb 15, 2023. doi: 10.4239/wjd.v14.i2.110
Protective effect of liraglutide on the myocardium of type 2 diabetic rats by inhibiting polyadenosine diphosphate-ribose polymerase-1
Dong-Dong Xue, Xiang Zhang, De-Wei Li, Yan-Lan Yang, Jing-Jin Liu
Dong-Dong Xue, Xiang Zhang, Jing-Jin Liu, Department of Endocrinology, Shanxi Provincial People's Hospital, Taiyuan 030000, Shanxi Province, China
De-Wei Li, Department of Thyroid Surgery, Shanxi Provincial People's Hospital, Taiyuan 030000, Shanxi Province, China
Yan-Lan Yang, Department of Endocrine, Shanxi Provincial People's Hospital, Taiyuan 030012, Shanxi Province, China
Author contributions: Xue DD and Zhang X contributed to the methodology; Yang YL and Liu JJ contributed to the writing original draft preparation; Li DW, Liu JJ contributed to the revising.
Supported by Shanxi Provincial Natural Science Foundation, No. 201701D121159; Shanxi Provincial Health and Family Planning Commission, No. 2014016; and Health Commission of Shanxi Province, No. 2019020.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals, protocol No. SYXK (Jin) 2018-1203, Animal Ethics Committee of Shanxi Provincial People's Hospital.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: The data to support the findings in the study are available from the corresponding author upon reasonable request.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jing-Jin Liu, MD, Technician, Department of Endocrinology, Shanxi Provincial People's Hospital, No. 29 Shuangta Street, Taiyuan 030012, Shanxi Province, China. liumeng237237@163.com
Received: September 16, 2022
Peer-review started: September 16, 2022
First decision: November 18, 2022
Revised: November 26, 2022
Accepted: December 21, 2022
Article in press: December 21, 2022
Published online: February 15, 2023
Processing time: 151 Days and 9.9 Hours
Abstract
BACKGROUND

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.

AIM

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.

METHODS

Forty healthy male SD rats aged 6 wk were randomly divided into two groups, a normal control group (n = 10) and a model group (n = 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.

RESULTS

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 (P < 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 (P < 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 (P < 0.05) but still higher than that in the normal control group.

CONCLUSION

Liraglutide may improve myocardial injury in type 2 diabetic rats by inhibiting the expression of myocardial PARP-1 in a dose-dependent manner.

Keywords: Liraglutide; animal models; Type 2 diabetic rats; Polyadenosine diphosphate-ribose polymerase-1; Haematoxylin and eosin staining; Immunohistochemistry

Core Tip: Low-dose streptozotocin combined with a high-glucose and high-fat diet can successfully establish a rat model of type 2 diabetes mellitus. After 4 wk of continuous feeding, myocardial injury can occur, which is consistent with diabetic cardiomyopathy. Liraglutide reduced the body weight of type 2 diabetic rats and significantly improved the fasting blood glucose and lipid profile in a dose-dependent manner. Liraglutide may improve myocardial injury in type 2 diabetic rats by inhibiting the expression of myocardial polyadenosine diphosphate-ribose polymerase-1 in a dose-dependent manner.