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 (n=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 (P<0.05), but there was no significant difference between groups A, B, and D (P>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 (P<0.05); there was significant difference between groups A and B (P<0.05), but no significant difference between groups C and D (P>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 (P<0.05), but there was no signifi-cant difference between groups B and D (P>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 (P<0.05), but there was no significant difference between groups C and D (P>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 (P<0.05), but there was no significant difference between groups A, B, and C (P>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 (P<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.
Renal dysfunction is one of the common perioperative complications of liver transplantation, involving the preoperative, intraoperative, and postoperative stages. Its occurrence is closely associated with multiple factors, including underlying liver disease, intraoperative hemodynamic instability, ischemia-reperfusion injury, and immunosuppressive therapy. Renal injury not only affects recipients’ short-term outcomes, but may also lead to long-term deterioration of renal function, increase the risk of chronic kidney disease, and exert a sustained negative impact on quality of life. Although postoperative immunosuppressive therapy can effectively prevent rejection, long-term use—particularly of calcineurin inhibitors—may cause substantial nephrotoxicity. In recent years, strategies that use combination immunosuppressive regimens to reduce/minimize calcineurin inhibitors exposure and thereby preserve renal function have attracted increasing attention. Mammalian target of rapamycin inhibitors, which are commonly used immunosuppressants after liver transplantation, play an important role in preventing rejection, reducing tumor recurrence, and preserving renal function. This consensus aims to standardize the use and management of mammalian target of rapamycin inhibitors in the prevention and treatment of renal injury after liver transplantation, provide scientific, standardized, and rational guidance for the clinical application of immunosuppressive regimens, reduce the incidence of renal dysfunction, and help improve the quality of life of liver transplant recipients.
