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胆红素对肾盂肾炎实验大鼠模型的保护作用。

Protective effects of bilirubin in an experimental rat model of pyelonephritis.

机构信息

Department of Pediatrics, Division of Nephrology, Dokuz Eylül University, İzmir, Turkey.

出版信息

Urology. 2012 Dec;80(6):1389.e17-22. doi: 10.1016/j.urology.2012.07.029. Epub 2012 Sep 18.

Abstract

OBJECTIVE

To investigate the effects of bilirubin in a rat model of pyelonephritis.

METHODS

Experimental pyelonephritis was induced in 32 wistar rats and 4 groups were formed: group 1 (no treatment), group 2 (antibiotic), group 3 (bilirubin), and group 4 (antibiotic + bilirubin). Antibiotic was given on days 3 to 8, and bilirubin was administered between days 0 and 8 of bacterial inoculation. Half of the rats were killed on the 9th day (early period) and histopathological parameters, immunohistochemical renal fibrosis markers, apoptosis, and oxidant/antioxidant system activities were evaluated. The rest of the rats were killed at the 6th week of the study and evaluated for histopathological parameters and renal fibrosis markers.

RESULTS

Inflammatory activity was significantly lower in rats treated with antibiotic + bilirubin vs no treatment group both in the early and late periods. In the late period, inflammatory cell intensity was lower in rats treated with bilirubin vs no treatment and the antibiotic + bilirubin groups. Interstitial fibrosis/tubular atrophy was lower in the antibiotic + bilirubin group vs the no treatment and antibiotic groups, and in bilirubin vs antibiotic group. Tissue inhibitor of metalloproteinase-1 expression was lower in the bilirubin vs antibiotic group. Terminal deoxynucleotidyl transferase mediated 2'-deoxyuridine, 5'-triphosphate nick end labeling(+) cells were significantly lower in bilirubin and antibiotic + bilirubin groups vs no treatment group. Malondialdehyde levels were significantly lower in the antibiotic + bilirubin vs the no treatment group and superoxide dismutase activity was significantly higher in the antibiotic and antibiotic + bilirubin groups vs the no treatment group.

CONCLUSION

Bilirubin may have protective effects on pyelonephritis-associated inflammation in both early and late periods in addition to fibrosis and apoptosis when applied with antibiotics. When used alone, bilirubin may also prevent inflammation (in the late period) and apoptosis.

摘要

目的

研究胆红素在肾盂肾炎大鼠模型中的作用。

方法

将 32 只 Wistar 大鼠诱导为实验性肾盂肾炎,并分为 4 组:第 1 组(无治疗)、第 2 组(抗生素)、第 3 组(胆红素)和第 4 组(抗生素+胆红素)。抗生素于第 3 天至第 8 天给予,胆红素于细菌接种的第 0 天至第 8 天给予。第 9 天(早期)处死一半大鼠,评估组织病理学参数、肾纤维化标志物的免疫组织化学、细胞凋亡和氧化应激/抗氧化系统活性。其余大鼠在研究的第 6 周被处死,并评估组织病理学参数和肾纤维化标志物。

结果

在早期和晚期,与无治疗组相比,抗生素+胆红素治疗的大鼠炎症活动明显降低。在晚期,与无治疗组和抗生素+胆红素组相比,胆红素治疗的大鼠炎症细胞强度较低。与无治疗组和抗生素组相比,抗生素+胆红素组的间质纤维化/肾小管萎缩较低,与抗生素组相比,胆红素组的组织抑制剂 1 表达较低。末端脱氧核苷酸转移酶介导的 2'-脱氧尿苷、5'-三磷酸末端标记(+)细胞在胆红素组和抗生素+胆红素组明显低于无治疗组。与无治疗组相比,抗生素+胆红素组的丙二醛水平显著降低,超氧化物歧化酶活性显著升高。

结论

胆红素与抗生素联合应用除了对纤维化和细胞凋亡有保护作用外,还可能对肾盂肾炎相关炎症具有早期和晚期的保护作用。单独使用时,胆红素也可能预防炎症(晚期)和细胞凋亡。

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