Pathophysiological characteristics of myocardium injury model in type 2 diabetic rats

Objective To explore the pathophysiological characteristics of myocardial injury model in type 2 diabetes mellitus (T2DM) induced by streptozotocin (STZ) injection after high-fat and high-sucrose feeding. Methods A total of 60 SD rats aged at 8-12 weeks and weighing 180-220 g were divided into normal (Nor) group (n=20), T2DM group (n=20) and insulin group (Ins, n=20) by random number table method. STZ was administrated to rats after 4 weeks of high fat and high sucrose diet or normal diet and followed by another 4 weeks of feeding with the same diet. Blood glucose and insulin levels were monitored, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Hemodynamic parameters were measured using an isolated cardiac perfusion model. The changes of mitochondrial structure were observed with transmission electron microscope. Mitochondrial respiratory function, activity of key enzymes in respiratory chain and ATP content were measured. One way ANOVA was used for statistical analysis. Results A total of 50 SD rats were finally enrolled in Nor group (n=20), T2DM group (n=15) or Ins group (n=15). The HOMA-IR index of T2DM and Ins group were higher than that of Nor group (4.2±0.4, 3.9±0.4, 1.4±0.3, respectively, F=312.3, P<0.01). The +dp/dt max of left ventricle [(3 599±215), (3 123±239), (3 084±200) mmHg/s, F=31.02, P<0.01] and left ventricular development pressure [(102±8), (89±6), (90±7) mmHg, F=14.19, P<0.01, 1 mmHg=0.133 kPa] were superior to those in T2DM group and Ins group. The mitochondrial respiration State 3, respiration control ratio and respiratory chain enzyme activity of Nor group were superior to those of Ins group and T2DM group (F=11.12-505.50, P<0.05); Nor group had more ATP production compared to the other two groups (P<0.01). Conclusion The modeling method used in this study provides the pathophysiologic characteristics of diabetes related myocardial, damages such as cardiac ventricular malfunction, mitochondrial dysfunction, energy metabolism abnormality, as well as hyperglycemia and insulin resistance, which can be used for the studies of cardioprotection of diabetic cardiomyopathy. Key words: Diabetes mellitus, type 2; Myocardium; Mitochondria