Fukuchi S G, Seeburger J L, Parquet G, Rolandelli R H
Department of Surgery, MCP, Hahnemann University, Philadelphia, USA.
J Surg Res. 1999 Jun 15;84(2):121-6. doi: 10.1006/jsre.1999.5626.
Administration of chemotherapeutic agents in the immediate postoperative period may have beneficial effects by decreasing local cancer recurrence rates, but this must be weighed against possible impairment of wound healing. Since local expression of transforming growth factor-beta1 (TGF-beta1) is normally upreglated following creation of experimental colonic anastomoses, this study examines the effects of 5-fluorouracil (5-FU) on colonic healing and on the local expression of TGF-beta1.
Forty-eight male Sprague-Dawley rats underwent transection of the descending colon with primary anastomosis and were then randomly assigned to receive either intraperitoneal 5-FU (20 mg/kg/day) or saline (SAL). On Postoperative Days (PODs) 3, 5, and 7, bursting pressure (BP, mm Hg) and bursting energy (BE, mm Hg xs) were determined in situ. Anastomotic and nonoperated segments of colon were harvested and analyzed using the semiquantitative reverse transcriptase-polymerase chain reaction to determine the relative expression of TGF-beta1 normalized to that of a constitutive gene.
Progressive increases in BP and BE were observed in both the 5-FU and the SAL groups, across the time course examined. Overall, these measures were decreased in the 5-FU groups compared to SAL, significantly so on PODs 5 and 7; BP, 127.8 +/- 7.6 vs 161.1 +/- 7.2 and 139.9 +/- 10.9 vs 186.0 +/- 8.6; BE, 1093.6 +/- 190.0 vs 2207.9 +/- 308.2, and 1518.5 +/- 326.5 vs 3279.3 +/- 225.7, respectively. Anastomotic TGF-beta1 expression also increased progressively in both groups over the postoperative time course. Expression in the 5-FU group, however, was significantly decreased compared to that in the SAL group on POD 3; 0.42 +/- 0.05 vs 0.84 +/- 0.04. Interestingly, this preceded the reduction in BP and BE in the 5-FU group on PODs 5 and 7. TGF-beta1 expression in nonoperated colonic segments did not change during the time points studied or in response to 5-FU administration.
Wound healing following a colonic anastomosis is associated with local increases in TGF-beta1 expression, which in turn is diminished by the administration of 5-FU. If this deleterious effect on wound healing could be counteracted, then chemotherapy administration in the immediate postoperative period may become safer.
在术后即刻给予化疗药物可能通过降低局部癌症复发率而产生有益效果，但这必须与伤口愈合可能受到的损害相权衡。由于在实验性结肠吻合术后，转化生长因子-β1（TGF-β1）的局部表达通常会上调，本研究探讨了5-氟尿嘧啶（5-FU）对结肠愈合及TGF-β1局部表达的影响。
48只雄性Sprague-Dawley大鼠接受降结肠横断并一期吻合，然后随机分为两组，分别腹腔注射5-FU（20mg/kg/天）或生理盐水（SAL）。在术后第3、5和7天，原位测定爆破压力（BP，mmHg）和爆破能量（BE，mmHg×s）。采集吻合段及未手术的结肠段，采用半定量逆转录聚合酶链反应分析，以确定TGF-β1相对于组成型基因的相对表达量。
在整个观察时间段内，5-FU组和SAL组的BP和BE均呈逐渐升高趋势。总体而言，5-FU组的这些指标低于SAL组，在术后第5天和第7天差异显著；BP分别为127.8±7.6 vs 161.1±7.2以及139.9±10.9 vs 186.0±8.6；BE分别为1093.6±190.0 vs 2207.9±308.2以及1518.5±326.5 vs 3279.3±225.7。两组吻合口处TGF-β1的表达在术后也均呈逐渐升高趋势。然而，在术后第3天，5-FU组的表达显著低于SAL组；分别为0.42±0.05 vs 0.84±0.04。有趣的是，这早于5-FU组在术后第5天和第7天BP和BE的降低。在研究的时间点内，未手术结肠段的TGF-β1表达未发生变化，也未因给予5-FU而改变。
结肠吻合术后的伤口愈合与局部TGF-β1表达增加有关，而5-FU的使用会降低这种表达。如果这种对伤口愈合的有害影响能够被抵消，那么术后即刻给予化疗可能会更安全。
