研究肾间质纤维化的肾缺血再灌注损伤梯度模型

IF 3.5 3区 医学
Fan Yang, Baoping Zhu, Elyce Ozols, Haitao Bai, Mengjie Jiang, Frank Y Ma, David J Nikolic-Paterson, Xiaoyun Jiang
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引用次数: 0

摘要

背景:从急性肾损伤发展为慢性肾病是一项重大的健康挑战。然而,现有的肾脏缺血再灌注(I/R)损伤动物模型的一个限制因素是,必须有严重的损伤,几乎达到危及生命的程度,才能引发随后的肾脏纤维化。因此,我们探索了一种诱导 I/R 损伤的适应性梯度方法,旨在促进肾脏纤维化的进展,同时保持肾脏的整体正常功能。研究方法每组使用 6-8 只雄性 C57BL/6 小鼠构建模型,所有小鼠均接受戊巴比妥钠麻醉并切除左肾。随后,在肾下支下方穿入一根丝线,通过滑轮系统在20克重物的拉力下将右肾升高,持续时间为30、40或60分钟。然后放下肾脏,缝合伤口,腹腔注射生理盐水。不同组别的小鼠在再灌注 1、3、7 或 28 天后安乐死。结果我们观察到高位肾脏下极血流完全停止,而上极血流不完全停止。在缺血 60 分钟的第 1 天,肾功能明显受损(正常人血清肌酐为 187.0 ± 65.3 vs 17.9 ± 4.8 μmol/L;p < .001),但在缺血 30 分钟或 40 分钟时,肾功能没有明显受损。第 1 天,下极和上极均出现明显的肾小管坏死和透明铸型形成。第 3 天,肾功能恢复正常,并在第 28 天保持正常。第 3 至 7 天,上极的组织学损伤消失,第 28 天组织学结果正常。相比之下,下极的肾小管损伤在第 3 天和第 7 天持续存在,到第 28 天时仍未缓解,并导致严重的肾纤维化。结论:我们创建了一个临床 "无声 "肾纤维化模型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A gradient model of renal ischemia reperfusion injury to investigate renal interstitial fibrosis.

Background: The progression from acute kidney injury to chronic kidney disease poses a significant health challenge. Nonetheless, a constraint in existing animal models of renal ischemia/reperfusion (I/R) injury is the necessity for a severe injury, almost reaching a life-threatening level, to trigger the subsequent onset of renal fibrosis. Hence, we explored an adapted gradient approach to induce I/R injury, aiming to promote the progression of renal fibrosis while preserving the overall normal functioning of the kidney. Methods: In each group, 6-8 male C57BL/6 mice were used for model construction, with all undergoing sodium pentobarbital anesthesia and left kidney removal. Subsequently, a silk thread was passed beneath the lower renal branch, elevating the right kidney under a 20-g weight's tension via a pulley system for durations of 30, 40, or 60 min. Afterwards, we lowered the kidney, sutured the wound, and administered intraperitoneal saline. Mice in different groups were euthanized following reperfusion for 1, 3, 7, or 28 days. Results: We observed a complete cessation of blood flow in the lower pole, while an incomplete cessation in the upper pole in the elevated kidney. Significant renal impairment was evident on day 1 with a 60min ischemic period (187.0 ± 65.3 vs 17.9 ± 4.8 μmol/L serum creatinine in normal; p < .001), but not with 30 or 40min. On day 1, tubular necrosis and hyaline cast formation was evident in both lower and upper poles. On day 3, renal function returned to normal and remained normal through day 28. Histologic damage resolved in the upper pole over days 3 to 7, resulting in normal histology on day 28. By contrast, there was sustained tubular damage tubular in the lower pole on days 3 and 7, which failed to resolve and led to significant renal fibrosis by day 28. Conclusion: We created a model demonstrating clinically "silent" renal fibrosis.

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来源期刊
International Journal of Immunopathology and Pharmacology
International Journal of Immunopathology and Pharmacology Immunology and Microbiology-Immunology
自引率
0.00%
发文量
88
期刊介绍: International Journal of Immunopathology and Pharmacology is an Open Access peer-reviewed journal publishing original papers describing research in the fields of immunology, pathology and pharmacology. The intention is that the journal should reflect both the experimental and clinical aspects of immunology as well as advances in the understanding of the pathology and pharmacology of the immune system.
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