Objective: To investigate the anti-apoptosis effect of intensive insulin treatment on cardiac myocytes and its underlying mechanism in severe scald rats.
Methods: Twelve SD rats were suffered from 30% TBSA full thickness scald, and they were divided into: IT group [with intravenous injection of isotonic saline including insulin (15 mU x kg(-1) x min(-1)) and 100 g/L glucose], B group [with treatment of isotonic saline (2 mL x kg(-1) x %TBSA(-1) x 8 h(-1)]. Six SD rats received sham burn as controls[sham(S)group, with treatment of fluid at physiologic dose]. + dp/ dtmax (the rate of the rise of left ventricular pressure) and -dp/ dtmax (the rate of the fall of left ventricular pressure)at 6 post burn hour (PBH)were recorded. Apoptosis were determined by TUNEL staining and DNA ladder. The phosphorylation f Akt and protein expression of Bcl-2 in cardiomyocyte were assayed by Western blotting.
Results: The + dp/ dtmax in the S group, IT group and B group at6 PBH were respectively (5.5 +/- 0.5) x 10(3) mm Hg/s, (3.4 +/- 0.4) x 10(3 mm Hg/s and (2.5 +/- 0.5) x 10(3) mm Hg/s (1 mm Hg = 0.133 kPa), the - dp/ dtmax were respectively (4.55 +/- 0.34) x 10(3) mmHg/s, (2.94 +/- 0.22) x 10(3) mm Hg/s and (2.05 +/- 0.19) x 10(3) mmHg/s.The +/- dp/dtmax in IT group was significantly higher than those in B group( P < 0.01). The apoptosis index in B group was (13.1 +/- 3.4)%, which was obviously higher than that in IT group (6.7 +/- 1.8)% and S group (0.6 +/- 0.4)% (P < 0.01). DNA ladder showed that no DNA fragmentation in S group, but obvious DNA fragmentation forming ladder pattern in B group, and no obvious ladder pattern in IT group. The phosphorylation of Akt and level of Bcl-2 protein in B group were markedly higher than those in IT group ( P < 0.05 or P < 0.01).
Conclusion: Intensive insulin treatment can upregulate the activity of Akt and enhance the expression of Bcl-2, and they might constitute the mechanisms for anti-apoptosis in cardiomyocyte and protection of cardiac function.