Human umbilical cord blood mononuclear cells protect against renal tubulointerstitial fibrosis in cisplatin-treated rats
Human umbilical cord blood mononuclear cells protect against renal tubulointerstitial fibrosis in cisplatin-treated rats
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人脐带血单核细胞可预防顺铂治疗的大鼠肾小管间质纤维化
DOI：
10.1016/j.biopha.2019.109310
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发表时间：
2020-01-01
影响因子：
7.5
通讯作者：
Duan, Shao-Bin
中科院分区：
文献类型：
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作者：
Li, Xu-Wei;Feng, Li-Xin;Duan, Shao-Bin
目前，尚无有效方法预防急性肾损伤（AKI）后肾间质纤维化。在本研究中，我们建立并筛选了一种新的顺铂诱导AKI后肾间质纤维化大鼠模型。我们的结果表明，在首次给予6.5 mg/kg负荷剂量的顺铂后，每周注射4 mg/kg顺铂一次，持续两周，可以建立更准确的反映AKI进展为肾间质纤维化的模型。然后，我们研究了人脐带血单核细胞（hUCBMNCs）对顺铂诱导的 AKI 后肾小管间质纤维化的影响和可能的机制。注射hUCBMNCs 4次的大鼠，血清和尿液中基质金属蛋白酶7（MMP-7）水平、尿白蛋白/肌酐比值、肾小管病理评分、肾小管间质区相对胶原面积、内质网扩张和线粒体超微结构损伤均显着改善。肾组织中活性氧、α-平滑肌肌动蛋白 (α-SMA)、[NOD] 样吡啶结构域蛋白 3 和 cleaved-Caspase 3 的水平显着降低。然而，在两次注射hUCBMNCs的大鼠中，MMP-7水平和尿白蛋白/肌酐比值没有发现显着差异。虽然注射两次hUCBMNCs的大鼠肾小管间质组织中α-SMA的表达和胶原染色的百分比面积有所改善，但其效果明显弱于注射四次hUCBMNCs的大鼠。综上所述，我们的研究构建了一种高效、可重复的顺铂诱导 AKI 后肾纤维化的新型大鼠模型。多次注射 hUCBMNC 可预防顺铂诱导的 AKI 后肾间质纤维化。
Currently, there is no effective method to prevent renal interstitial fibrosis after acute kidney injury (AKI). In this study, we established and screened a new renal interstitial fibrosis rat model after cisplatin-induced AKI. Our results indicated that rats injected with 4 mg/kg cisplatin once a week for two weeks after firstly administrated with 6.5 mg/kg loading dose of cisplatin could set up a more accurate model reflecting AKI progression to renal interstitial fibrosis. Then, we investigated the effects and possible mechanisms of human umbilical cord blood mononuclear cells (hUCBMNCs) on renal tubular interstitial fibrosis after cisplatin-induced AKI. In rats injected with hUCBMNCs for four times, level of matrix metalloproteinase 7(MMP-7) in serum and urine, urinary albumin/creatinine ratio, tubular pathological scores, the relative collagen area of the tubulointerstitial region, endoplasmic reticulum dilation and the mitochondrial ultrastructural damage were significantly improved. The level of reactive oxygen species, alpha-smooth muscle actin (alpha-SMA), [NOD]-like pyrin domain containing protein 3 and cleaved-Caspase 3 in renal tissue decreased significantly. However, in rats injected with hUCBMNCs for two times, no significant difference was discovered in MMP-7 levels and urinary albumin/creatinine ratio. Although expression of alpha-SMA and the percentage areas of collagen staining in tubulointerstitial tissues were ameliorated in rats injected with hUCBMNCs for two times, the effects were significantly weaker than those in rats injected with hUCBMNCs for four times. Taken together, our study constructed a highly efficient, duplicable novel rat model of renal fibrosis after cisplatin-induced AKI. Multiple injections of hUCBMNCs may prevent renal interstitial fibrosis after cisplatin-induced AKI.