Protective effect of insulin on myocardial ischemia-reperfusion injury in diabetic rats based on PI3K/Akt signaling pathway
10.3760/cma.j.issn.1008-1372.2019.03.012
- VernacularTitle:基于PI3K/Akt信号通路研究胰岛素对糖尿病大鼠心肌缺血再灌注损伤的保护作用
- Author:
Jin YANG
1
;
Shuigen MA
;
Zhaojun XU
;
Zhi LIU
;
Guangsheng NI
Author Information
1. 湖南中医药大学第一附属医院心胸外科
- Keywords:
1-phosphatidylinositol 3-kinase;
Protein kinases;
Insulin;
Diabetes mellitus;
Reperfusion injury;
Rats
- From:
Journal of Chinese Physician
2019;21(3):364-367,372
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect of insulin on phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway in diabetic rats with myocardial ischemia reperfusion injury.Methods Diabetic rats were induced by high-sugar and high-fat diet plus intraperitoneal injection of streptozotocin (40 mg/kg).They were randomly divided into diabetic sham group (group A),diabetes ischemic reperfusion group (group B),diabetes ischemic reperfusion insulin treatment group (group C) and diabetic ischemia reperfusion + insulin Wortmaninn (PI3K inhibitors) group (group D),10 in each group.Myocardial ischemia reperfusion model in diabetic rats:heart was exposed between the third and fourth ribs of the left chest,2 mm from the lower edge of the left atrial ear,and 5-0 sterile suture was used to ligate the anterior descending coronary artery (LAD) and the great cardiac vein for 30 min,and then the perfusion was resumed for 120 min.Wortmannin (15 μg/kg) was given through femoral vein 20 min before ligation in group D,and the same amount of normal saline was given in the other 3 groups.Insulin (2 U/kg) was injected subcutaneously in group C and D 10 min before ligation,and the same amount of normal saline was injected subcutaneously in group A and group B.Plasma creatine kinase MB (CK-MB)and troponin Ⅰ (cTnⅠ) levels were measured in arterial blood after 120 min of reperfusion,and PI3K and Akt expression in myocardial tissue were detected by Western blot.Results Compared with the group A,the plasma levels of cTnI and CK-MB increased and the expressions of PI3K and phosphorylated protein kinase B (p-Akt) in myocardium decreased in the group B (P ＜ 0.05).After insulin treatment,the plasma cTnI [(0.89 ± 0.26) μg/L],CK-MB [(9.24 ±3.16) μg/L] in the myocardial tissue of the group C decreased,while the expression of PI3K (0.341 8 ±0.03 1) and p-Akt (0.673 1 ±0.028) in the myocardial tissue increased (P ＜0.05).After insulin + Wortmaninn administration,the plasma cTnI [(1.16 ±0.29) μg/L] and CK-MB [(12.57 ± 3.01) μg/L] in the group D increased,while the expression of PI3K (0.292 7 ± 0.036) and p-Akt (0.531 4 ± 0.030) in the myocardial tissue decreased,with statistically significant difference (P ＜ 0.05).Conclusions Insulin can reduce serum CK-MB and cTnⅠ levels in diabetic rats with myocardial ischemia reperfusion injury,possibly by activating PI3K/Akt signal transduction pathway,inhibiting myocardial enzyme release,and improving myocardial ischemia reperfusion injury in diabetic rats to play a protective role in myocardial cells.
