Effects of glycyl-glutamine dipeptide supplementation on myocardial damage and cardiac function in rats after severe burn injury

Abstract

Glutamine decreases myocardial damage in ischemia/reperfusion injury. However, the cardioprotective effect of glutamine after burn injury remains unclear. Present study was to explore the protective effect of glycyl-glutamine dipeptide on myocardial damage in severe burn rats. Seventy-two Wistar rats were randomly divided into three groups: normal control (C), burned control (B) and glycyl-glutamine dipeptide-treated (GG) groups. B and GG groups were inflicted with 30% total body surface area of full thickness burn. The GG group was given 1.5 g/kg glycyl-glutamine dipeptide per day and the B group was given the same dose of alanine via intraperitoneal injection for 3 days. The serum CK, LDH, AST, and, blood lactic acid levels, as well as the myocardium ATP and GSH contents, were measured. The indices of cardiac contractile function and histopathological change were analyzed at 12, 24, 48, and 72 post-burn hours (PBH). The serum CK, LDH, AST and blood lactic acid levels increased, and the myocardium ATP and GSH content decreased in both burned groups. Compared with B group, the CK, LDH, AST and blood lactic acid levels reduced, myocardium ATP and GSH content increased in GG group. Moreover, the inhibition of cardiac contractile function and myocardial histopathological damage were reduced significantly in GG group. We conclude that myocardial histological structure and function were damaged significantly after burn injury, glycyl-glutamine dipeptide supplementation is beneficial to myocardial preservation by improving cardiocyte energy metabolism, increasing ATP and glutathione synthesis.

Keywords: GSH; Glycyl-glutamine dipeptide; burns; energy metabolism; myocardial damage; rat.

Figure 1

Cardiac pathological change with Gly-Gln dipeptide treatment after burn injury (HE stain, 200x). A. Cardiac apex of the B group at 12 PBH; B. cardiac apex of the GG group at 12 PBH; C. cardiac apex of the B group at 24 PBH; D. cardiac apex of the GG group at 24 PBH.

Figure 2

Water content changes of myocardial tissue at 12, 24, 48 and 72 PBH. Data are mean±S.D. Repeated measures analysis of variance was performed and Dunn-Šidàk adjustment for pairwise contrasts are preferred in the tests of multiple pairwise comparisons of repeated measurements , **P < 0.01 compared with the C group; #P < 0.05, ##P < 0.01 compared with the B group.

Figure 3

Effect of Gly-Gln dipeptide treatment on myocardial zymogram activities at 12, 24, 48 and 72 PBH. Changes in the activities of various indices: A. CK; B. LDH; and C. AST. Data are mean±S.D. (n = 6 per group). Repeated measures analysis of variance was performed and Dunn-Šidàk adjustment for pairwise contrasts are preferred in the tests of multiple pairwise comparisons of repeated measurements **P < 0.01 compared with the C group; #P < 0.05, ##P < 0.01 compared with the B group.

Figure 4

Effect of Gly-Gln dipeptide treatment on lactic acid content in blood at 12, 24, 48 and 72 PBH. Data are mean±S.D. (n = 6 per group). Repeated measures analysis of variance was performed and Dunn-Šidàk adjustment for pairwise contrasts are preferred in the tests of multiple pairwise comparisons of repeated measurements, *P < 0.05, **P < 0.01 compared with the C group; ##P < 0.01 compared with the B group.

Figure 5

Effect of Gly-Gln dipeptide treatment on myocardial ATP content at 12, 24, 48 and 72 PBH. Data are mean±S.D. (n = 6 per group). Repeated measures analysis of variance was performed and Dunn-Šidàk adjustment for pairwise contrasts are preferred in the tests of multiple pairwise comparisons of repeated measurements *P < 0.05, **P < 0.01 compared with the C group; #P < 0.05, ##P < 0.01 compared with the B group.

Figure 6

Effect of Gly-Gln dipeptide treatment on myocardial GSH content at 12, 24, 48 and 72 PBH. Data are mean±S.D. (n = 6 per group). Repeated measures analysis of variance was performed and Dunn-Šidàk adjustment for pairwise contrasts are preferred in the tests of multiple pairwise comparisons of repeated measurements **P < 0.01 compared with the C group; ##P < 0.01 compared with the B group.

Figure 7

Effect of Gly-Gln dipeptide treatment on cardiac function at 12, 24, 48 and 72 PBH. Changes in the various cardiac function indices: (A) AOSP; (B) AODP; (C) LVSP; and (D) +dp/dt_max. Data are mean±S.D. (n = 6 per group). Repeated measures analysis of variance was performed and Dunn-Šidàk adjustment for pairwise contrasts are preferred in the tests of multiple pairwise comparisons of repeated measurements *P < 0.05,**P < 0.01 compared with the C group; #P < 0.05,##P < 0.01 compared with the B group.