Guler Sanem, Cimen Sertac, Hu Qianni, Venkatachalam Ananda Baskaran, Hart-Matyas Michael, Alwayn Ian
a Department of Surgery, Queen Elizabeth II Health Sciences Centre , Dalhousie University , Halifax , Nova Scotia , Canada.
b Atlantic Centre for Transplantation Research , Dalhousie University , Halifax , Nova Scotia , Canada.
J Invest Surg. 2016 Oct;29(5):275-81. doi: 10.3109/08941939.2016.1149643. Epub 2016 Mar 16.
Postsurgical adhesions can occur after laparotomy and can cause morbidity. Local delivery of sirolimus prevented adhesion formation in various experiments. We analyzed the impact of orally dosed mammalian target of rapamycin inhibitors on abdominal adhesion formation and wound tensile strength in an experimental model.
Wistar albino rats were divided into sirolimus, everolimus, and control groups (n = 6 per group). Experimental animals underwent midline laparotomy and adhesion induction procedure which included cecum abrasion and mesh implantation. Animals were administered oral sirolimus (4 mg/kg), everolimus (3 mg/kg), or placebo starting on postoperative day 1. Treatments were given until postoperative day 7. At postoperative day 21, adhesions were scored. Meshes were resected with the attached abdominal wall and cecal segment and stained with Sirius red for collagen density analysis. Midline scars were excised for tensile strength measurement. Effects of sirolimus and everolimus on fibroblast proliferation were also assessed.
Mean adhesion score of the everolimus group (7.83 ± 1.17) was significantly lower compared to sirolimus (11.00 ± 0.63) and control (11.66 ± 0.51) groups. Mean collagen density of the everolimus group (33.5 ± 7.8) was significantly lower compared to sirolimus (50.7 ± 9.69) and control (53.8 ± 12.4) groups. Mean tensile strength of the control group (26.41 ± 2.10) was significantly higher compared to sirolimus (17.89 ± 1.9) and everolimus (21.37 ± 1.25) groups. It was significantly lower in sirolimus group than everolimus group. Both sirolimus and everolimus treated media inhibited fibroblast proliferation significantly compared to media alone.
Everolimus effectively reduced adhesions. Nevertheless, it also reduced wound tensile strength: an effect which seemed to be due to inhibition of fibroblast proliferation.
剖腹手术后可能会形成手术粘连并导致发病。在各种实验中，西罗莫司的局部递送可预防粘连形成。我们在一个实验模型中分析了口服雷帕霉素抑制剂对腹部粘连形成和伤口抗张强度的影响。
将Wistar白化大鼠分为西罗莫司组、依维莫司组和对照组（每组n = 6）。实验动物接受中线剖腹术和粘连诱导程序，包括盲肠擦伤和植入网片。从术后第1天开始，给动物口服西罗莫司（4mg/kg）、依维莫司（3mg/kg）或安慰剂。治疗持续至术后第7天。在术后第21天，对粘连进行评分。切除带有附着的腹壁和盲肠段的网片，并用天狼星红染色以进行胶原密度分析。切除中线瘢痕以测量抗张强度。还评估了西罗莫司和依维莫司对成纤维细胞增殖的影响。
依维莫司组的平均粘连评分（7.83±1.17）明显低于西罗莫司组（11.00±0.63）和对照组（11.66±0.51）。依维莫司组的平均胶原密度（33.5±7.8）明显低于西罗莫司组（50.7±9.69）和对照组（53.8±12.4）。对照组的平均抗张强度（26.41±2.10）明显高于西罗莫司组（17.89±1.9）和依维莫司组（21.37±1.
