链脲佐菌素诱导2型糖尿病大鼠的心肌损伤观察及机制初探

目的观察链脲佐菌素（STZ）诱导2型糖尿病后不同时期大鼠心肌损伤及凋亡的程度，并对其机制进行分析。方法使用高糖、高脂加STZ注射造成大鼠2型糖尿病模型，于STZ注射后不同时间点分批处死动物，对心肌损伤及凋亡指标进行测定。结果糖尿病大鼠经STZ处理1周后，与对照组大鼠相比，空腹血糖明显升高（FBG≥16．7mmol／L），而血清胰岛素含量升高或无明显变化，提示2型糖尿病造模成功。糖尿病大鼠第12周起LVSP、＋dp／dtmax、-dp／dtmax显著降低，提示糖尿病可引起心功能下降。糖尿病大鼠第2周、4周和12周CK—MB明显增高，第12周和24周cTnI明显增高，提示糖尿病第2周即可诱发心肌损伤，并随着病程的发展加重。凋亡指标测定表明，糖尿病大鼠在第4周和12周时，caspase-3和caspase-8活性显著增高，第12周和24周时caspase-9活性显著增高，提示糖尿病第4周即可造成心肌细胞凋亡，且可能依赖caspase-8途径早于依赖caspase-9途径。结论糖尿病可以引起心肌损伤和细胞凋亡，并随病程的延长而加重，这种凋亡与caspase-8和caspase-9依赖的凋亡途径有关。

Research of mechanisms of myocardial injury and apoptosis in streptozotocin-induced type 2 diabetic rats

Objective To observe the extent of myocardial injury and apoptosis in streptozotocin （STZ） induced type 2 diabetic rats at different time points, and to analyze its possible mechanisms. Methods After successful establishment of type 2 diabetic model of rats with a high-sugar and high-fat diet and STZ injection, the rats were sacrificed in batches and the indicators for myocardial injury and cell apoptosis were measured. Results After one week STZ treatment, the level of blood glucose in diabetic rats was significantly higher （FBG≥16.7 mmol/L） than that of the control group, while with an increased or unchanged insulin level, which suggested that the type 2 diabetic rats model was successfully established. The level of LVSP, ＋ dp/dtmax, -dp/dtmax in diabetic rats was significantly decreased from the 12th week, and this indicated that the cardiac function was decreased. In diabetic rats, the level of CK-MB was significantly increased in the 2nd, 4th and 12th week,and the cTnI level was significantly increased in the 12th and 24th week, which suggested that diabetes may induce myocardial injury from the 2nd week, and it was aggravatod with the development of the disease. Results of apoptotic index measurement showed that the activity of caspase-3 and caspase-8 was significantly increased in the 4th and 12th week in diabetic rats, whereas caspase-9 activity was significantly increased in the 12th and 24th week. This indicated that diabetes may cause cardiomyoeyte apoptosis from the 4th week, and rely on caspase-8 pathway superior to caspase-9 pathway. Conclusion Diabetes may cause myocardial injury and apoptosis, and the extent of which was aggravated with the development of the disease. Cardiomyocyte apoptosis are mainly induced through caspase-8- and caspase-9-dependent pathways.