| Summary: | 碩士 === 長庚大學 === 基礎醫學研究所 === 92 === Wound healing is a complex process consisting of inflammation(macrophage and neutrophil), granulation tissue(fibroblasts), and tissue remodeling phase(tissue repair). Oxidative stress (e.g., reactive oxygen species or ROS production) may play a complex role during wound healing. Matrix metalloprotinase-8 (MMP-8) is important to degrade extracellular matrix to facilitate repair process and that ROS can influence MMP-8 expression. In this study, we intend to explore the roles of ROS production and MMP-8 in an excision wound model of rat by treating trolox (an water-soluble antioxidant) treatment for different durations. We also examined the morphological changes and wound closure rate at 3,5,7,10,and 14-day following the wound.
Two durations of antioxidant treatment (trolox; 0.1 mM 1.5 mL per rat) were employed：early (starting 6h post-wound and followed by daily supplement of trolox) and late (starting 3d post-wound and followed by daily supplement) phase for 14 days. We determined the relative wound closure area (%), ROS production of wound tissue (CPS/mg tissue), morphology of the wound tissues (H&E stain, 10 section), capillary density, and MMP-8 expression of the wound tissue.
We found that late trolox group exhibited the fastest healing process, significantly more % closure than control and early group at 4th- and 5th- d. Stained sections demonstrated a well-developed granulation tissue, more capillaries (7th-d), and a sign of complete healing with hair follicles at 14th-d. Late trolox treatment shifted the peak of ROS production forward to the 5th-d and significantly reduced ROS production at 7th-day by 3/4. We further found that MMP-8 content decreased more than that of control at 5th-d. Thus, late trolox treatment appears to be beneficial to wound healing.
In early trolox group, the healing process was apparently slowed down and less complete (lower capillary density and no hair follicles). ROS production was also reduced early on (3rd-d) and MMP-8 level was lowered even earlier (<1d). These results indicate that early inhibition of ROS and MMP-8 were not associated with promoting wound healing.
Taken together, ROS production appeared to play different roles during healing process. Late trolox (>3d) apparently improved wound healing while early trolox (>6th-h ) did not. A very low early MMP-8 concentration, observed in early trolox group, was not associated with improved healing. These data suggest a complex role of oxidative stress for wound healing, dependent on the temporal appearance of the ROS production during the various phases of the healing process.
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