[Effects of rapamycin and deferoxamin on wound healing after ischemia and hypoxia].

Objective: To explore the effect and mechanism of rapamycin and deferoxamin on wound healing after ischemia and hypoxia.

Methods: The model of ischemia and hypoxia wound was made on the back of 40 SPF male adult Sprague Dawley rats, weight (300±20) g; they were randomly divided into 4 groups ( =10): the control group (group A), deferoxamine intervention group (group B), rapamycin intervention group (group C), and deferoxamine+rapamycin intervention group (group D). At 3, 6, and 9 days after model preparation, rats of groups A, B, C, and D were intra-peritoneally injected with normal saline, deferoxamin (10 mg/kg), rapamycin (3 mg/kg), deferoxamin (10 mg/kg)+rapamycin (3 mg/kg) respectively. The wound healing was observed and the healing time was recorded in each group; the wound healing tissue was harvested to test the mRNA and protein expressions of mammalian target of rapamycin (mTOR), hypoxia inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF) by real-time fluorescence quantitative PCR and Western blot at 2 days after wound healing.

Results: All rats survived to the end of the experiment, and wounds healed; the healing time of groups A, B, and D was significantly shorter than that of group C ( <0.05), but there was no significant difference between groups A, B, and D ( >0.05). Real-time fluorescence quantitative PCR showed that the expression of mTOR mRNA in groups C and D was significantly decreased when compared with the expressions in groups A and B ( <0.05); there was significant difference between groups A and B ( <0.05), but no significant difference between groups C and D ( >0.05). The expressions of HIF-1α mRNA and VEGF mRNA were signi-ficantly higher in groups B and D than groups A and C, and in group A than group C ( <0.05), but there was no signifi-cant difference between groups B and D ( >0.05). Western blot showed that the relative expressions of mTOR protein in groups C and D were significantly decreased when compared with the expressions in groups A and B ( <0.05), but there was no significant difference between groups C and D ( >0.05). The relative expressions of HIF-1α protein in groups A, B, and C were significantly increased when compared with expression in group D ( <0.05), but there was no significant difference between groups A, B, and C ( >0.05). The relative expression of VEGF protein were significantly lower in groups B, C, and D than group A, in group D than groups B and C, and in group C than group B ( <0.05).

Conclusion: Defe-roxamin can promote the wound healing of rats after ischemia and hypoxia, and the effect of rapamycin is opposite. It may be related to the existence of mTOR and HIF-1 signaling pathway in chronic ischemia-hypoxia wound.