他克莫司对植入Walker 256癌肉瘤的Wistar大鼠肾脏的作用。

Action of tacrolimus on Wistar rat kidneys implanted with Walker 256 carcinosarcoma.

作者信息

Inácio Cristiano Machado, Dietz Ulrich Andréas, Malafaia Osvaldo, Ribas Filho Jurandir Marcondes, Nassif Paulo Afonso Nunes, Czeczko Nicolau Gregori, Marcondes Carmen Australia Paredes

机构信息

Evangelic Faculty of Parana, University Evangelic Hospital, Curitiba, PR, Brazil.

出版信息

Acta Cir Bras. 2010 Feb;25(1):98-104. doi: 10.1590/s0102-86502010000100020.

DOI:10.1590/s0102-86502010000100020

PMID:20126896

Abstract

PURPOSE

To evaluate the development of Walker 256 tumor in male Wistar rats treated with tacrolimus using an experimental kidney tumor model.

METHODS

40 male Wistar rats were divided into four groups: Tumor group (TU) (n=10), Tacrolimus-Tumor group (TT) (n=10), Tacrolimus group (TC) (n=10) and Control group (C) (n=10). Treatment with tacrolimus was performed in groups TT and TC. Under anesthesia, the right kidney of each animal of TU and TT was accessed through a supraumbilical incision and inoculated with a 0.1 mL solution containing 2 x 10(6) tumor cells (Walker 256 carcinosarcoma tumor cells). Group TC was treated with a saline solution. All the animals of groups TC and TT were treated with tacrolimus (5mg/kg/day) by gavage for 15 days. TU group animals received saline by gavage for 15 days. On the 15th postoperative day, all animals were submitted to euthanasia and blood sampling for analysis of serum creatinine (Cr) and blood urea nitrogen (BUN). Abdominal gross examination was performed, the right kidney removed and prepared for histological analysis by hematoxylin-eosin staining. The resulting data were submitted to statistical analysis by ANOVA.

RESULTS

Statistical significance was found when comparing creatinine level between groups TU, TT and TC -TT group culminated with a marked increased in creatinine levels (Cr=1.013 + or - 0.3028 mg/mL), TU group (Cr=0.5670 + or - 0.03536 mg/dL) P=0.00256, TC group (Cr =0.711 + or - 0.1653 mg/mL) P= 0.02832. Statistical significance was found when comparing BUN levels in TT group (71.32 + or - 17.14 mg/mL), compared with TU group (45.83 + or - 5.046 mg/dL), P=0.000318. There were no statistically significant differences between groups TT and TC (61.23 + or - 9.503 mg/mL) P=0.7242. Histological analysis showed a poor evolution in TT group with multiple foci of hemorrhage and cortical invasion by the Walker tumor.

CONCLUSION

The Tacrolimus-treated group developed a more aggressive tumor and a drug-related nephrotoxic effect.

摘要

目的

使用实验性肾肿瘤模型评估用他克莫司治疗的雄性Wistar大鼠中Walker 256肿瘤的发展情况。

方法

将40只雄性Wistar大鼠分为四组：肿瘤组（TU）（n = 10）、他克莫司-肿瘤组（TT）（n = 10）、他克莫司组（TC）（n = 10）和对照组（C）（n = 10）。TT组和TC组用他克莫司进行治疗。在麻醉下，通过脐上切口进入TU组和TT组每只动物的右肾，并接种0.1 mL含2×10⁶肿瘤细胞（Walker 256癌肉瘤肿瘤细胞）的溶液。TC组用生理盐水溶液治疗。TC组和TT组的所有动物通过灌胃给予他克莫司（5mg/kg/天），持续15天。TU组动物通过灌胃给予生理盐水，持续15天。在术后第15天，所有动物进行安乐死并采血，用于分析血清肌酐（Cr）和血尿素氮（BUN）。进行腹部大体检查，取出右肾并通过苏木精-伊红染色制备用于组织学分析。将所得数据通过方差分析进行统计分析。

结果

比较TU组、TT组和TC组之间的肌酐水平时发现有统计学意义——TT组最终肌酐水平显著升高（Cr = 1.013±0.3028 mg/mL），TU组（Cr = 0.5670±0.03536 mg/dL），P = 0.00256，TC组（Cr = 0.711±0.1653 mg/mL），P = 0.02832。比较TT组（71.32±17.14 mg/mL）与TU组（45.83±5.046 mg/dL）的BUN水平时发现有统计学意义，P = 0.000318。TT组和TC组之间（61.23±9.503 mg/mL）无统计学显著差异，P = 0.7242。组织学分析显示TT组进展较差，有多个出血灶且Walker肿瘤侵犯皮质。