Vasiliadis K, Pramateftakis M G, Blouhos K, Mantzoros I, Koliakos G, Zaraboukas T, Kanellos I, Demetriades H, Alamdari D H, Betsis D
Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Dis Colon Rectum. 2007 Jun;50(6):899-907. doi: 10.1007/s10350-006-0878-6.
This experimental study was designed to investigate whether iloprost can reverse impaired colonic healing caused by immediate postoperative intraperitoneal administration of 5-fluorouracil plus leucovorin.
Eighty Wistar rats were randomized into four groups. After resection of a 1-cm segment of transverse colon, an end-to-end sutured anastomosis was generated. Rats received saline solution (Group 1), 5-fluorouracil plus leucovorin (Group 2), iloprost (Group 3), and 5-fluorouracil plus leucovorin plus iloprost (Group 4) intraperitoneally from the day of operation and once daily until killing. Each group was further randomized into two subgroups. Subjects were killed on the fifth (Subgroup a) and eighth (Subgroup b) postoperative days. After killing, anastomoses were examined macroscopically and graded histologically. Rats were measured for anastomotic bursting pressures and tissue hydroxyproline levels.
The leakage rate of the anastomoses was significantly higher in the 5-fluorouracil plus leucovorin group compared with the other groups (P = 0.049). Bursting pressure was significantly lower in 2a subgroup (5-fluorouracil plus leucovorin, postoperative Day 5) than in 4a (5-fluorouracil plus leucovorin plus iloprost, postoperative Day 5; P < 0.001). Adhesion formation was significantly higher in all b subgroups compared with the Control b subgroup. Neoangiogenesis was significantly higher in iloprost and iloprost plus 5-fluorouracil plus leucovorin subgroups compared with the 5-fluorouracil plus leucovorin subgroups. Hydroxyproline levels, collagen deposition, fibroblasts, and white cell count were significantly higher in the iloprost plus 5-fluorouracil plus leucovorin b subgroup (postoperative Day 8) compared with the 5-fluorouracil plus leucovorin b subgroup (postoperative Day 8).
The immediate postoperative, intraperitoneal administration of iloprost counteracts and reverses the negative effects of 5-fluorouracil plus leucovorin chemotherapy and protects colonic healing in rats.
本实验研究旨在探讨伊洛前列素能否逆转术后即刻腹腔注射5-氟尿嘧啶加亚叶酸钙所导致的结肠愈合受损。
80只Wistar大鼠被随机分为四组。横结肠切除1厘米节段后，进行端端缝合吻合。从手术当天起，大鼠腹腔内注射生理盐水（第1组）、5-氟尿嘧啶加亚叶酸钙（第2组）、伊洛前列素（第3组）以及5-氟尿嘧啶加亚叶酸钙加伊洛前列素（第4组），每日一次，直至处死。每组再进一步随机分为两个亚组。在术后第5天（亚组a）和第8天（亚组b）处死动物。处死动物后，对吻合口进行宏观检查并进行组织学分级。测量大鼠吻合口破裂压力和组织羟脯氨酸水平。
与其他组相比，5-氟尿嘧啶加亚叶酸钙组吻合口漏出率显著更高（P = 0.049）。2a亚组（5-氟尿嘧啶加亚叶酸钙，术后第5天）的破裂压力显著低于4a亚组（5-氟尿嘧啶加亚叶酸钙加伊洛前列素，术后第5天；P < 0.001）。与对照b亚组相比，所有b亚组的粘连形成显著更多。与5-氟尿嘧啶加亚叶酸钙亚组相比，伊洛前列素组以及伊洛前列素加5-氟尿嘧啶加亚叶酸钙亚组的新生血管形成显著更多。与5-氟尿嘧啶加亚叶酸钙b亚组（术后第8天）相比，伊洛前列素加5-氟尿嘧啶加亚叶酸钙b亚组（术后第8天）的羟脯氨酸水平、胶原沉积、成纤维细胞和白细胞计数显著更高。
术后即刻腹腔注射伊洛前列素可抵消并逆转5-氟尿嘧啶加亚叶酸钙化疗的负面影响，并保护大鼠结肠愈合。
