Gaber M W, Aziz A M, Shang X, Penmetsa R, Sabek O M, Yen M R T, Gaber L W, Moore L W, Gaber A O
University of Tennessee Health Science Center, Memphis Tennessee 38138, USA.
Transplant Proc. 2006 Dec;38(10):3331-2. doi: 10.1016/j.transproceed.2006.10.047.
Wound healing complications have been observed in patients receiving sirolimus (SLR). This study examined the degree and duration of delayed healing in various protocols using SLR. Sprague-Dawley rats underwent a standard midline abdominal incision and wound closure. Groups of 6 rats each were randomized to receive different doses of SLR (2 and 5 mg/kg) with or without loading dose (10 mg/kg x3 days), and with or without steroids (20 mg/kg x3 days followed by 5 mg/kg for 2 weeks). Rats were humanely killed on postoperative days 5, 10, or 15. Wound breaking force was measured using the EHMI BIAX-II instrument and tensile strength was calculated. Wounds in control animals had gradual increase in tensile strength during the 15-day observation. In contrast, high and loading doses of SLR caused reduction in wound strength until day 10, but the wounds' tensile strength became equivalent to control by day 15. The addition of steroids prolonged wound recovery with low doses of SLR until day 15 and had very profound effects on healing in high-dose SLR-treated animals (>50% reduction) that continued beyond the 2 weeks of observation. Low doses of SLR in non-steroid-treated animals had a short-term (5-day) impact on wound healing; high dose and loading doses delayed healing for 10 to 15 days. The addition of steroids had a synergistic effect on delayed wound healing, particularly in animals receiving high-dose SLR, which demonstrated prolonged wound weakness. These results may provide practical guidelines for postoperative introduction of SLR in the context of various clinical protocols.
在接受西罗莫司（SLR）治疗的患者中观察到了伤口愈合并发症。本研究考察了使用SLR的各种方案中延迟愈合的程度和持续时间。将Sprague-Dawley大鼠进行标准的腹部正中切口并缝合伤口。每组6只大鼠，随机接受不同剂量的SLR（2和5mg/kg），有或无负荷剂量（10mg/kg×3天），以及有或无类固醇（20mg/kg×3天，随后2周为5mg/kg）。在术后第5、10或15天对大鼠实施安乐死。使用EHMI BIAX-II仪器测量伤口破裂力并计算抗张强度。在15天的观察期内，对照动物的伤口抗张强度逐渐增加。相比之下，高剂量和负荷剂量的SLR会导致伤口强度在第10天之前降低，但到第15天时伤口的抗张强度与对照相当。添加类固醇会延长低剂量SLR处理的伤口恢复时间至第15天，并且对高剂量SLR处理的动物（降低>50%）的愈合有非常显著的影响，这种影响在观察的2周之后仍持续存在。在未用类固醇处理的动物中，低剂量的SLR对伤口愈合有短期（5天）影响；高剂量和负荷剂量会使愈合延迟10至15天。添加类固醇对延迟伤口愈合有协同作用，特别是在接受高剂量SLR的动物中，表现出伤口虚弱持续时间延长。这些结果可能为在各种临床方案中术后引入SLR提供实用指南。
