Objective To observe the diverse apoptosis of the myocardiac mitochondria on insulin therapy in diabetic rats and to investigate the anti-apoptotic mechanism of insulin interacting with the mitochondria.
Methods Male wistar rats were administered with intraperitoneal injection of streptozotocin (STZ, 25 mg/kg) and high fat diet to induce type 2 diabetic mellitus. Twenty-two were randomly divided into two treatment groups, namely, the early treatment group and the late treatment group (each n=7), and one diabetic (DM)group (n=8). Another eight were chosen for control. Novolin 30R was administrated hypodermically to the early treatment group (IE group) at the first week and to the late treatment group (IL group) at the fourth week. DM group were injected subcutaneously with physiological saline. All groups were treated for 8 weeks. At the end of the experiment we compared SOD, MDA, GSH in different groups, as well as apoptotic index, mitochondrial membrane potential (ΔΨm), active oxygen and myocardial ultrastructure.
Results Compared to the control group, DM rats had higher blood glucose (30.53±2.39 vs 7.48±1.03, p<0.01), HW/BW (2.88±0.01 vs 2.56±0.03, p<0.05), MDA (6.46±0.99 vs 4.98±0.30, p<0.01), apoptotic index (0.934±0.032 vs 0.063±0.011, p<0.01), and active oxygen, but lower SOD (222.06±12.94 vs 245.99±8.67, p<0.01), GSH (6.99±1.50 vs 9.71±0.67, p<0.01) and ΔΨm (0.243±0.087 vs 0.900±0.075, p<0.01). The mitochondrial crista of DM rats break, dissolved and became vacuolous. Compared to the DM group, The level of MDA (5.31±0.60 vs 6.46±0.99, p<0.01) and apoptotic index (0.48±0.07 vs 0.93±0.03, p<0.01) were significantly lower and the level of ΔΨm (0.63±0.09 vs 0.24±0.09, p<0.01) was increaseed in the IE group. The IE group showed remarkable improvement in contrast to the IL group which improved a little (MDA (5.31±0.60 vs 6.27±0.75, p<0.01), apoptotic index (0.48±0.07 vs 0.90±0.03, p<0.01), ΔΨm (0.63±0.09 vs 0.35±0.04, p<0.01).
Conclusion Insulin has an anti-apoptotic effect on cardiocytes of diabetic rats, and earlier intervention is better than later.
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