Kucuk Hasan Fehmi, Bingul Sadik Mehmet, Kurt Necmi, Kaptanoglu Levent, Akyol Huseyin, Torlak Oguzhan Aziz, Colak Elif
Kartal Research and Education Hospital, Istanbul, Turkey.
Eur Surg Res. 2006;38(5):451-7. doi: 10.1159/000095088. Epub 2006 Aug 15.
Scarring is one of the steps of excessive wound healing, causing dysfunction of the involved tissues and clinically poor cosmetics. The aim of this study was to examine the effect of a highly selective cyclooxygenase-2 (COX-2) inhibitor on renal scar formation in experimental pyelonephritis.
Four groups of 10 Balb/C mice were formed. In groups I and II following the inoculation of lipopolysaccharide (LPS) into both kidneys, 0.18 and 0.36 mg/day of rofecoxib was given respectively via intraperitoneal route for 5 days. No medication was applied following physiological saline solution injection to both kidneys of the mice in group III (negative control group). After group IV's LPS inoculation on the first day, saline solution (1 ml/day) was given intraperitoneally for 5 days (positive control group). Following the exposure of both kidneys, LPS of Escherichia coli (5 mg/kg) was injected into the kidneys of groups I, II, and IV. In group III, saline solution (0.1 ml) was used instead of LPS. Three days after the inoculation of LPS, solutions containing 0.18 and 0.36 mg of COX-2 inhibitor were given intraperitoneally for 5 days in groups I and II. No medication was used for the mice in group III. Six weeks after the inoculation of LPS and saline solution, all mice were humanely euthanized. Bilateral nephrectomies were done on each group of mice, and histopathological examination was performed.
Inoculation of LPS into the renal parenchyma caused pyelonephritis and scar formation in all groups. The degree of pyelonephritis and scar formation was lesser in groups in which COX-2 inhibitors were used. The degree of scar formation was lesser in group II, in which 0.36 mg more of COX-2 inhibitor was used than in group I (0.18 mg of COX-2 inhibitor).
In our study model, direct inoculation of LPS to kidneys caused experimentally induced pyelonephritis. Renal scar formation was effectively prevented through the utilization of rofecoxib at 0.36-mg doses.
瘢痕形成是伤口过度愈合的一个阶段,会导致受累组织功能障碍且临床美观效果不佳。本研究旨在探讨一种高选择性环氧化酶-2(COX-2)抑制剂对实验性肾盂肾炎肾瘢痕形成的影响。
将40只Balb/C小鼠分为四组,每组10只。在第I组和第II组中,双侧肾脏接种脂多糖(LPS)后,分别通过腹腔途径给予0.18毫克/天和0.36毫克/天的罗非昔布,持续5天。第III组小鼠双侧肾脏注射生理盐水后未用药(阴性对照组)。第IV组在第一天接种LPS后,腹腔注射生理盐水(1毫升/天),持续5天(阳性对照组)。暴露双侧肾脏后,向第I、II和IV组的肾脏注射大肠杆菌LPS(5毫克/千克)。在第III组中,用生理盐水(0.1毫升)代替LPS。接种LPS三天后,第I组和第II组腹腔注射含0.18毫克和0.36毫克COX-2抑制剂的溶液,持续5天。第III组小鼠未用药。接种LPS和生理盐水六周后,对所有小鼠实施安乐死。对每组小鼠进行双侧肾切除术,并进行组织病理学检查。
向肾实质接种LPS导致所有组出现肾盂肾炎和瘢痕形成。使用COX-2抑制剂的组中,肾盂肾炎和瘢痕形成的程度较轻。第II组瘢痕形成程度较轻,该组使用的COX-2抑制剂比第I组(0.18毫克COX-2抑制剂)多0.36毫克。
在我们的研究模型中,向肾脏直接接种LPS可导致实验性肾盂肾炎。使用0.36毫克剂量的罗非昔布可有效预防肾瘢痕形成。