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Mar Drugs
2018 Jan 08;161:. doi: 10.3390/md16010016.
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Effect of Low Molecular Weight Oligopeptides Isolated from Sea Cucumber on Diabetic Wound Healing in db/db Mice.
Li D
,
Li L
,
Xu T
,
Wang T
,
Ren J
,
Liu X
,
Li Y
.
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Impaired wound healing is a major clinical problem in patients with diabetes and is the leading cause of lower limb amputation. This study is aimed to observe the effects of small molecule oligopeptides isolated from sea cucumber (SCCOPs) on the wound healing process in diabetic mice. Ninety db/db male mice were divided into five groups, including the model control group, whey protein group (0.50 g/kg) and three SCCOPs dose groups (0.25 g/kg, 0.50 g/kg and 1.00 g/kg). Additionally, 18 db/m male mice were used as normal control group. After full-thickness incisions on the dorsum, mice in SCCOPs-treated groups were intragastrically administered SCCOPs, while others were administered vehicle or whey protein. Mice were sacrificed on days 4, 7 and 14. The wound healing condition, inflammatory response, angiogenesis, collagen deposition, oxidative stress and nutritional status were evaluated. A pathological report showed increased vascularisation, collagen deposition and epithelialisation in SCCOPs-treated groups. SCCOPs-treated mice showed decreased C-reactive protein (CRP), interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, chemokine (C-C motif) ligand 2 (CCL2) and reactive oxygen species (ROS) contents, and increased IL-10, stromal cell-derived factor-1 alpha (SDF-1α), nitric oxide (NO), albumin (ALB), prealbumin (PA) and transferrin (TRF) levels and vascular endothelial growth factor (VEGF) expression. All parameters were significant (p < 0.05) in comparison to model control group. These results suggest that treatment with SCCOPs can promote significant wound healing in diabetic mice.
Figure 1. Representative macroscopic images of wounds in mice on days 4, 7 and 14. (SCCOPs, small molecule oligopeptides isolated from sea cucumber; NC, normal control group; MC, model control group; WP, 0.50 g/kg whey protein group; SCCOPs-L, 0.25 g/kg SCCOPs group; SCCOPs-M, 0.50 g/kg SCCOPs group; SCCOPs-H, 1.00 g/kg SCCOPs group).
Figure 2. Representative micrograph of haematoxylin and eosin-stained section of wounds in mice on days 4, 7 and 14. The incision site in MC showed irregular arrangement of collagen bundles were loosely packed, and wounds demonstrated decreased vascularisation and epithelialisation. The site of wounds in SCCOPs-treated mice showed more densely packed and compactly arranged collagen bundles with increased blood vessel formation and on-going epithelialisation, reflecting a more rapidly healing wound than that of MC. (Magnification, 40× and 200×; SCCOPs, small molecule oligopeptides isolated from sea cucumber; NC, normal control group; MC, model control group; WP, 0.50 g/kg whey protein group; SCCOPs-L, 0.25 g/kg SCCOPs group; SCCOPs-M, 0.50 g/kg SCCOPs group; SCCOPs-H, 1.00 g/kg SCCOPs group).
Figure 4. Serum IL-6 (A), IL-8 (B), TNF-α (C), CCL2 (D) and IL-10 (E) content in mice on days 4, 7 and 14. (IL-6, interleukin-6; IL-8, interleukin-8; TNF-α, tumor necrosis factor-α; CCL2, chemokine (C-C motif) ligand 2; IL-10, interleukin-10; SCCOPs, small molecule oligopeptides isolated from sea cucumber; NC, normal control group; MC, model control group; WP, 0.50 g/kg whey protein group; SCCOPs-L, 0.25 g/kg SCCOPs group; SCCOPs-M, 0.50 g/kg SCCOPs group; SCCOPs-H, 1.00 g/kg SCCOPs group). Values are presented as mean ± SD. Values are presented as mean ± SD. * p < 0.05 versus NC, # p < 0.05 versus MC, ∆ p < 0.05 versus WP.
Figure 6. Expression of VEGF in wound tissue on day 14 after wounding in (a) NC; (b) MC; (c) WP; (d) SCCOPs-L; (e) SCCOPs-M and (f) SCCOPs-H. The VEGF immunolabeling was striking in SCCOPs-treated groups, whereas it was faint in MC and WP. (Magnification, 200×; VEGF, vascular endothelial growth factor; SCCOPs, small molecule oligopeptides isolated from sea cucumber; NC, normal control group; MC, model control group; WP, 0.50 g/kg whey protein group; SCCOPs-L, 0.25 g/kg SCCOPs group; SCCOPs-M, 0.50 g/kg SCCOPs group; SCCOPs-H, 1.00 g/kg SCCOPs group).
Figure 8. Collagen accumulation in wound areas in mice. (A) representative high power view light micrographs (Masson’s trichrome staining) in (a) NC, (b) MC, (c) WP, (d) SCCOPs-L, (e) SCCOPs-M and (f) SCCOPs-H on day 14 (Magnification, 200×); (B) hydroxyproline levels in the incision wound tissue in mice on days 4, 7 and 14. (SCCOPs, small molecule oligopeptides isolated from sea cucumber; NC, normal control group; MC, model control group; WP, 0.50 g/kg whey protein group; SCCOPs-L, 0.25 g/kg SCCOPs group; SCCOPs-M, 0.50 g/kg SCCOPs group; SCCOPs-H, 1.00 g/kg SCCOPs group). Values are presented as mean ± SD. Values are presented as mean ± SD. * p < 0.05 versus NC, # p < 0.05 versus MC, ∆ p < 0.05 versus WP.
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