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生长激素对腹腔注射5-氟尿嘧啶、博来霉素和顺铂后结肠吻合口的影响:一项实验研究。

Effect of growth hormone on colonic anastomosis after intraperitoneal administration of 5-fluorouracil, bleomycin and cisplatin: An experimental study.

作者信息

Lambrou Ioannis, Mantzoros Ioannis, Ioannidis Orestis, Tatsis Dimitrios, Anestiadou Elissavet, Bisbinas Vasiliki, Pramateftakis Manousos-Georgios, Kotidis Efstathios, Driagka Barbara, Kerasidou Ourania, Symeonidis Savvas, Bitsianis Stefanos, Sifaki Freideriki, Angelopoulos Konstantinos, Demetriades Haralabos, Angelopoulos Stamatios

机构信息

Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece.

Department of ENT, Royal Cornwall Hospitals NHS Trust, Cornwall TR1 3LJ, United Kingdom.

出版信息

World J Gastrointest Surg. 2024 Aug 27;16(8):2679-2688. doi: 10.4240/wjgs.v16.i8.2679.

Abstract

BACKGROUND

Growth hormone (GH) plays a crucial role in wound healing and tissue repair in postoperative patients. In particular, colonic anastomosis healing following colorectal surgery is impaired by numerous chemotherapy agents.

AIM

To investigate whether GH can improve the healing of a colonic anastomosis following the adverse effects of intraperitoneal administration of 5-fluorouracil (5-FU), bleomycin and cisplatin.

METHODS

Eighty Wistar rats underwent laparotomy and a 1 cm-resection of the transverse colon, followed by an end-to-end anastomosis under general anesthesia. The rats were blindly allocated into four equal groups and administered a different daily intraperitoneal therapeutic regimen for 6 days. The control group (A) received normal saline. Group B received chemotherapy with 5-FU (20 mg/kg), bleomycin (4 mg/kg) and cisplatin (0.7 mg/kg). Group C received GH (2 mg/kg), and group D received the aforementioned combination chemotherapy and GH, as described. The rats were sacrificed on the 7 postoperative day and the anastomoses were macroscopically and microscopically examined. Body weight, bursting pressure, hydroxyproline levels and inflammation markers were measured.

RESULTS

All rats survived until the day of sacrifice, with no infections or other complications. A decrease in the body weight of group D rats was observed, not statistically significant compared to group A ( = 1), but significantly different to groups C ( = 0.001) and B ( < 0.01). Anastomotic dehiscence rate was not statistically different between the groups. Bursting pressure was not significantly different between groups A and D ( = 1.0), whereas group B had a significantly lower bursting pressure compared to group D ( < 0.001). All groups had significantly more adhesions than group A. Hydroxyproline, as a measurement of collagen deposition, was significantly higher in group D compared to group B ( < 0.05), and higher, but not statistically significant, compared to group A. Significant changes in group D were recorded, compared to group A regarding inflammation (3.450 2.900, = 0.016) and fibroblast activity (2.75 3.25, = 0.021). Neoangiogenesis and collagen deposition were not significantly different between groups A and D. Collagen deposition was significantly increased in group D compared to group B ( < 0.001).

CONCLUSION

Intraperitoneal administration of chemotherapy has an adverse effect on the healing process of colonic anastomosis. However, GH can inhibit the deleterious effect of administered chemotherapy agents and induce colonic healing in rats.

摘要

背景

生长激素(GH)在术后患者的伤口愈合和组织修复中起着关键作用。特别是,结直肠手术后的结肠吻合口愈合会受到多种化疗药物的损害。

目的

研究生长激素是否能改善腹腔注射5-氟尿嘧啶(5-FU)、博来霉素和顺铂的不良反应后结肠吻合口的愈合情况。

方法

80只Wistar大鼠接受剖腹手术,横结肠切除1cm,然后在全身麻醉下进行端端吻合。将大鼠随机分为四组,每组数量相等,每天给予不同的腹腔内治疗方案,持续6天。对照组(A组)给予生理盐水。B组接受5-FU(20mg/kg)、博来霉素(4mg/kg)和顺铂(0.7mg/kg)的化疗。C组给予生长激素(2mg/kg),D组给予上述联合化疗和生长激素。术后第7天处死大鼠,对吻合口进行宏观和微观检查。测量体重、破裂压力、羟脯氨酸水平和炎症标志物。

结果

所有大鼠均存活至处死日,无感染或其他并发症。观察到D组大鼠体重下降,与A组相比无统计学意义(P = 1),但与C组(P = 0.001)和B组(P < 0.01)有显著差异。各组间吻合口裂开率无统计学差异。A组和D组的破裂压力无显著差异(P = 1.0),而B组的破裂压力显著低于D组(P < 0.001)。所有组的粘连均显著多于A组。作为胶原蛋白沉积指标的羟脯氨酸,D组显著高于B组(P < 0.05),与A组相比更高,但无统计学意义。与A组相比,D组在炎症(3.450 ± 2.900,P = 0.016)和成纤维细胞活性(2.75 ± 3.25,P = 0.021)方面有显著变化。A组和D组之间的新生血管形成和胶原蛋白沉积无显著差异。D组的胶原蛋白沉积与B组相比显著增加(P < 0.001)。

结论

腹腔内化疗对结肠吻合口的愈合过程有不良影响。然而,生长激素可以抑制所用化疗药物的有害作用,并诱导大鼠结肠愈合。

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