Abstract：
BACKGROUND: Many experimental studies have examined multiple drugs or treatments to improve the healing of intestinal anastomoses. Synthetic prostacyclin analogs, immunosuppressants, erythropoietin, growth hormone, insulin-like growth factor type 1, synthetic metalloproteinases inhibitors, and hyperbaric oxygen therapy have produced promising results in low-risk models of anastomosis dehiscence. However, in high-risk models, only hyperbaric oxygen therapy has been shown to be useful. Pirfenidone (PFD), a commonly used antifibrosing drug, has not been shown to be effective for this purpose. Our objective was to evaluate the effects of PFD on anastomosis healing and adhesion genesis in a low-risk rat model of dehiscence of colonic anastomosis.
METHODS: An experimental study was conducted on 40 healthy Wistar rats randomly assigned to the control group or PFD experimental group (20 rats in each group). Colon anastomosis was performed 3 cm above the peritoneal reflection using the same technique in all animals. Mechanical resistance was studied by measuring bursting pressure. Adhesions were evaluated macroscopic and histologically using common staining techniques. Animals received the first PFD dose 12 h after surgery at a dose of 500 mg/kg one a day (SID) for 5 consecutive days. On day 6, the animals were reoperated on to measure the bursting pressure in situ and to classify adhesions macroscopically, and the anastomosed colon was resected for histological analysis.
RESULTS: There were no deaths, complications, or anastomosis dehiscence in either group. The mean bursting pressure was 120.8 ± 11 mm Hg and 135.5 ± 12.4 in the control and PFD groups, respectively (p < 0.001). The adhesions were less dense and had less inflammatory cell infiltration in the PFD group (p < 0.02 and 0.002, respectively). Collagen content was slightly higher in the PFD group (p = 0.04).
CONCLUSIONS: Our results revealed favorable effects of PFD in this low-risk colon anastomosis model; for example, the bursting pressure was higher, and the macroscopic adhesions were soft and exhibited less inflammatory infiltration and higher collagen content in the PFD group than in the control group. The results showing that PFD treatment was associated with better healing of minor adhesions seem to be paradoxical because the therapeutic indications for this drug are directed at treating fibrosing diseases.
METHODS: An experimental study was conducted on 40 healthy Wistar rats randomly assigned to the control group or PFD experimental group (20 rats in each group). Colon anastomosis was performed 3 cm above the peritoneal reflection using the same technique in all animals. Mechanical resistance was studied by measuring bursting pressure. Adhesions were evaluated macroscopic and histologically using common staining techniques. Animals received the first PFD dose 12 h after surgery at a dose of 500 mg/kg one a day (SID) for 5 consecutive days. On day 6, the animals were reoperated on to measure the bursting pressure in situ and to classify adhesions macroscopically, and the anastomosed colon was resected for histological analysis.
RESULTS: There were no deaths, complications, or anastomosis dehiscence in either group. The mean bursting pressure was 120.8 ± 11 mm Hg and 135.5 ± 12.4 in the control and PFD groups, respectively (p < 0.001). The adhesions were less dense and had less inflammatory cell infiltration in the PFD group (p < 0.02 and 0.002, respectively). Collagen content was slightly higher in the PFD group (p = 0.04).
CONCLUSIONS: Our results revealed favorable effects of PFD in this low-risk colon anastomosis model; for example, the bursting pressure was higher, and the macroscopic adhesions were soft and exhibited less inflammatory infiltration and higher collagen content in the PFD group than in the control group. The results showing that PFD treatment was associated with better healing of minor adhesions seem to be paradoxical because the therapeutic indications for this drug are directed at treating fibrosing diseases.
摘要：
背景：许多实验研究已经检查了多种药物或治疗方法以改善肠吻合的愈合。合成前列环素类似物，免疫抑制剂,促红细胞生成素,生长激素,胰岛素样生长因子1,合成金属蛋白酶抑制剂,和高压氧疗法在低风险的吻合口裂模型中产生了有希望的结果。然而,在高风险模型中，只有高压氧治疗被证明是有用的。吡非尼酮(PFD),一种常用的抗纤维化药物，没有被证明是有效的。我们的目的是评估低风险大鼠结肠吻合裂开模型中PFD对吻合愈合和粘连发生的影响。
方法：对40只健康Wistar大鼠进行实验研究，随机分为对照组或PFD实验组（每组20只）。在所有动物中使用相同的技术在腹膜反射上方3cm处进行结肠吻合。通过测量爆破压力研究了机械阻力。使用常见的染色技术在宏观和组织学上评估粘连。动物在手术后12小时以每天500mg/kg的剂量(SID)接受第一PFD剂量,连续5天。在第6天，对动物进行再次手术以测量原位破裂压力并对粘连进行宏观分类。切除吻合的结肠进行组织学分析。
结果：没有死亡，并发症,或吻合口开裂。对照组和PFD组的平均爆破压力为120.8±11mmHg和135.5±12.4，分别(p<0.001)。PFD组的粘连密度较低，炎性细胞浸润较少（分别为p<0.02和0.002）。PFD组的胶原含量稍高(p=0.04)。
结论：我们的结果揭示了PFD在这种低危结肠吻合模型中的有利作用；例如，爆破压力较高,与对照组相比，PFD组的宏观粘连柔软，炎症浸润少，胶原含量高。显示PFD治疗与较小粘连的更好愈合相关的结果似乎是矛盾的，因为该药物的治疗适应症旨在治疗纤维化疾病。
方法：对40只健康Wistar大鼠进行实验研究，随机分为对照组或PFD实验组（每组20只）。在所有动物中使用相同的技术在腹膜反射上方3cm处进行结肠吻合。通过测量爆破压力研究了机械阻力。使用常见的染色技术在宏观和组织学上评估粘连。动物在手术后12小时以每天500mg/kg的剂量(SID)接受第一PFD剂量,连续5天。在第6天，对动物进行再次手术以测量原位破裂压力并对粘连进行宏观分类。切除吻合的结肠进行组织学分析。
结果：没有死亡，并发症,或吻合口开裂。对照组和PFD组的平均爆破压力为120.8±11mmHg和135.5±12.4，分别(p<0.001)。PFD组的粘连密度较低，炎性细胞浸润较少（分别为p<0.02和0.002）。PFD组的胶原含量稍高(p=0.04)。
结论：我们的结果揭示了PFD在这种低危结肠吻合模型中的有利作用；例如，爆破压力较高,与对照组相比，PFD组的宏观粘连柔软，炎症浸润少，胶原含量高。显示PFD治疗与较小粘连的更好愈合相关的结果似乎是矛盾的，因为该药物的治疗适应症旨在治疗纤维化疾病。
