Zinc deficiency impairs wound healing of colon anastomosis in rats.
BACKGROUND
Anastomotic leakage is a relevant surgical complication. The aim of the study was to investigate the influence of a controlled preoperative zinc deficiency on the extracellular matrix composition of colon anastomosis.


METHODS
Forty male Wistar rats were randomized to either a zinc deficiency group (n = 20) or a control group (n = 20). In each animal, a transverse colonic end-to-end anastomosis was performed. On postoperative day 7, the surface of the mucosal villi, expression of matrix metalloproteinases (MMP) 2, 8, 9, and 13, and both the number of proliferating cells (Ki67) and apoptotic cells, as well as the collagen types I/III ratio were analyzed. Within the anastomotic area the mesenterial region and the antimesenterial region were analyzed separately.


RESULTS
In each group, one anastomotic leakage was detected. Expression of both MMP 2, 9, and 13 was significantly higher, and expression of Ki67 was significantly reduced in the zinc deficient group both mesenterial and antimesenterial. The collagen types I/III ratio was reduced in the zinc deficiency group by trend, without statistical significance neither mesenterial nor antimesenterial. Likewise, zinc deficiency affected neither the expression of MMP 8 nor the rate of apoptotic cells, respectively. Analyses of the surface of the mucosal villi revealed no significant differences comparing the groups with neither mesenterial nor antimesenterial.


CONCLUSIONS
Our study constitutes the known negative effect of zinc deficiency on wound healing. Zinc deficiency significantly increased the activity of MMPs (2, 9, and 13), caused a reduced collagen type I/III ratio, and delayed cell proliferation and quality of intestinal wound healing.
Department of Surgery, RWTH Aachen University Hospital, Pauwelsstr 30, 52074 Aachen, Germany. mbinneboesel@ukaachen.de
Marcel
M
Binnebösel
Jochen
J
Grommes
Benita
B
Koenen
Karsten
K
Junge
Christian D
CD
Klink
Michael
M
Stumpf
Alexander P
AP
Ottinger
Volker
V
Schumpelick
Uwe
U
Klinge
Carsten J
CJ
Krones
D000714:Anastomosis, Surgical; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D003106:Colon / Q000378:metabolism / Q000601:surgery*; D003677:Deficiency Diseases / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013536:Suture Techniques; D013997:Time Factors; D014945:Wound Healing; D015032:Zinc / Q000097:blood / Q000172:deficiency*
D024042:Collagen Type I; D024061:Collagen Type III; D017364:Collagenases; D015032:Zinc