Effects of Albumin Infusion on Serum Levels of Albumin, Proinflammatory Cytokines (TNF- α, IL-1, and IL-6), CRP, and MMP-8; Tissue Expression of EGRF, ERK1, ERK2, TGF- β, Collagen, and MMP-8; and Wound Healing in Sprague Dawley Rats

Abstract

In this study, we sought to determine the roles of albumin in wound healing, which is infused both pre- and postoperatively in malnourished patients presenting with hypoalbuminemia. For the purposes of the study, we used 25 male Sprague Dawley rats of predetermined weight and age, which were initially maintained in a standard environment and fed the same diet for 7 days prior to being segregated into one of the following five groups: A, control, normal protein feed (20% casein); B, hypoalbuminemia, 25% rat albumin infusion prior to surgery; C, hypoalbuminemia, normal protein feed (20% casein); D, hypoalbuminemia, 25% rat albumin infusion after surgery; and E, hypoalbuminemia, low-protein feed (casein 2%). The animals in all five groups were subjected to four deep incisions in their dorsal muscle fascia. On days 1, 3, 5, and 7 after surgery, ELISA was used to determine serum levels of TNF-α, IL-1, IL-6, CRP, and MMP-8, whereas immunohistochemistry was used to determine the tissue expression of EGFR, ERK1, ERK2, TGF-β, collagen, and MMP-8. Significant reductions in serum levels of TNF-α, IL-1, and CRP were detected in the groups receiving albumin infusion and the high-casein diet (P < 0.05). The administration of albumin and a high-casein diet also increased the tissue expression of EGFR, ERK1, ERK2, TGF-β, and collagen and decreased that of MMP-8 relative to the hypoalbuminemia control (P < 0.05). We propose that the administration of albumin promoted NF-κB signaling which, in turn, induced the transduction and transcription of factors involved in wound healing. Albumin infusion and dietary proteins play vital roles in accelerating the wound healing process, as they can contribute to correcting the hypoalbuminemic state. These findings provide insights that will contribute to our understanding of wound healing, particularly in malnourished patients.

Figure 1

(a) Incision location. (b) Visitrek.

Figure 2

Expression of ERK1 on 5 wound tissue specimens in groups A, B, C, D, and E at the 5^th day. Note. Brown color represented the expression of ERK1 phospho (pointed out with the black arrow), while transparency showed that there was not any ERK1 expression.

Figure 3

Expression of ERK2 on 5 wound tissue specimens in groups A, B, C, D, and E at the 5^th day. Note. Brown color represented the expression of ERK2 phospho (pointed out with the black arrow), while transparency showed that there was not any ERK2 expression.

Figure 4

Expression of TGF-β on 5 wound tissue specimens in groups A, B, C, D, and E at the 5^th day. Note. Brown color represented the expression of TGF-β phospho (pointed out with the black arrow), while transparency showed that there was not any TGF-β expression.

Figure 5

Expression of MMP-8 on 5 wound tissue specimens in groups A, B, C, D, and E at the 5^th day. Note. Brown color represented the expression of MMP-8 phospho (pointed out with the black arrow), while transparency showed that there was not any MMP-8 expression.

Figure 6

Graphs of EGFR (a), ERK1 (b), ERK2 (c), TGF-β (d), collagen (e), and MMP-8 (f) and wound tissue on day 1, 3, 5, and 7 in groups A, B, C, D, and E.

Figure 7

Expression of collagen on 5 wound tissue specimens in groups A, B, C, D, and E at the 5^th day. Note. Brown color represented the expression of collagen phospho (pointed out with the black arrow), while transparency showed that there was not any collagen expression.

Figure 8

Expression of EGFR phospho on 5 wound tissue specimens in groups A, B, C, D, and E at the 5^th day. Note. Brown color represented the expression of EGFR phospho (pointed out with the black arrow), while transparency showed that there was not any EGFR expression.

Figure 9

Graph of wound healing processes in group A, B, C, D, and E after surgery.