术前放疗与手术相结合可抑制大鼠局部胶原蛋白和转化生长因子-β1的积累。

Combination of pre-operative radiotherapy and surgery suppresses local accumulation of collagen and TGF-beta1 in rats.

作者信息

Johnson Louis B, Adawi Diya, Agren Magnus S, Jorgensen Lars N, Wittgren Lena, Mattsson Sören, Blomquist Peter, Gottrup Finn, Jeppsson Bengt

机构信息

Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.

出版信息

J Surg Res. 2006 Jun 15;133(2):136-42. doi: 10.1016/j.jss.2005.12.012. Epub 2006 Feb 3.

DOI:10.1016/j.jss.2005.12.012

PMID:16458927

Abstract

BACKGROUND

The systemic and local tissue repair responses of radiation in combination with surgery are still unclear. We have studied the effect of fractionated pre-operative radiotherapy with or without subsequent laparotomy on collagen accumulation using a rodent model.

MATERIALS AND METHODS

Thirty-two male Sprague-Dawley rats were divided into four groups (eight rats per group): 1) sham radiation and sham laparotomy (control); 2) sham radiation and laparotomy; 3) radiation and sham laparotomy; and 4) radiation followed by laparotomy. Expanded polytetrafluoroethylene (ePTFE) tubes were implanted subcutaneously in the abdominal wall in the radiotherapy field and on the back outside the radiotherapy field day 0. The abdomen (3 cm x 4 cm) was irradiated day 3 (10 Gy) and again day 7 (10 Gy). On day 10, implants were extirpated, laparotomy undertaken in groups 2 and 4 and new ePTFE tubes implanted subcutaneously. The second implants were extirpated on day 20. Implants were analyzed for hydroxyproline, total protein and transforming growth factor-beta1 (TGF-beta1) levels.

RESULTS

On day 10, hydroxyproline (P < 0.05) and TGF-beta1 (P < 0.001) were lower in ePTFE tubes in irradiated compared with non-irradiated rats. On day 20, the abdominal ePTFE hydroxyproline remained low (P < 0.001) in animals subjected to laparotomy and pre-operative irradiation while hydroxyproline levels of rats subjected to irradiation only were similar to controls. The effects of radiation on hydroxyproline were confined to the irradiated abdominal area. There was a positive correlation between hydroxyproline and TGF-beta1 levels in the abdominal wall implant day 20 (r = 0.53, P < 0.005).

CONCLUSION

A clinically relevant fractionated radiation scheme reduced subcutaneous collagen accumulation pre-operatively and profoundly within the radiation field post-operatively after laparotomy, possibly because of lowered TGF-beta1 levels.

摘要

背景

放疗联合手术的全身及局部组织修复反应仍不明确。我们使用啮齿动物模型研究了分次术前放疗（无论后续是否行剖腹术）对胶原积累的影响。

材料与方法

32只雄性斯普拉格-道利大鼠分为四组（每组8只）：1）假放疗及假剖腹术（对照组）；2）假放疗及剖腹术；3）放疗及假剖腹术；4）放疗后行剖腹术。在放疗区域的腹壁及放疗区域外的背部皮下于第0天植入膨体聚四氟乙烯（ePTFE）管。于第3天（10 Gy）和第7天（10 Gy）对腹部（3 cm×4 cm）进行照射。在第10天，取出植入物，对第2组和第4组进行剖腹术，并再次皮下植入新的ePTFE管。在第20天取出第二次植入物。分析植入物中的羟脯氨酸、总蛋白和转化生长因子-β1（TGF-β1）水平。

结果

在第10天，与未照射大鼠相比，照射大鼠的ePTFE管中羟脯氨酸（P < 0.05）和TGF-β1（P < 0.001）水平较低。在第20天，接受剖腹术及术前照射的动物腹部ePTFE中的羟脯氨酸水平仍然较低（P < 0.001），而仅接受照射的大鼠的羟脯氨酸水平与对照组相似。放疗对羟脯氨酸的影响局限于照射的腹部区域。在第20天腹壁植入物中，羟脯氨酸与TGF-β1水平呈正相关（r = 0.53，P < 0.005）。