| 摘要: |
| 目的:探讨肾损伤生物标志物在评估钙调磷酸酶抑制剂(CNI)相关肾损伤中的价值。方法:构建阿霉素肾病综合征大鼠模型,随机分为4 组:空白对照组、激素对照组、激素+环孢素(CsA)组和激素+他克莫司(FK506) 组,统计分析4 组大鼠在不同治疗时间点(7、14、21 d)血液及尿液中肾损伤生物标志物[中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肾损伤分子-1(KIM-1)、白细胞介素-18(IL-18)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β( TGF-β)] 水平以及肾组织病理变化情况。结果:CNI 治疗早期肾脏并未出现明显病理损伤,CNI 治疗中期开始出现肾损伤,并且随着治疗时间延长肾损伤逐渐加重,激素+CsA 组损伤比激素+FK506 组更严重,差异有统计学意义(P<0. 05);CNI 治疗早中期NGAL、TNF-α 和IL-18 出现变化,CNI 治疗后期TGF-β 出现变化,与激素对照组比较差异均有统计学意义(P<0. 05);激素+CsA 组的NGAL 水平与肾小管间质损伤病理评分呈正相关(P<0. 05)。结论:NGAL、TNF-α 和IL-18 是评估CNI 治疗早中期相关肾损伤的敏感指标,TGF-β 对于CNI 治疗后期相关肾损伤具有更好的预警价值;NGAL 水平与CsA 相关肾损伤病理评分具有更好的相关性。 |
| 关键词: 肾损伤生物标志物 环孢素 他克莫司 肾损伤 |
| DOI：10.13407/j.cnki.jpp.1672-108X.2024.12.001 |
|
| 基金项目: |
|
| Value of Biomarkers for Kidney Injury in Evaluating Calcineurin Inhibitors-Associated Kidney Injury |
| Zhu Yan, Li Zhi, Zhang Bin, Hao Sheng, Kang Yulin, Huang Wenyan, Wu Ying |
| (Shanghai Children’s Hospital,School of Medicine, Shanghai Jiao Tong University, Shanghai Children’s Hospital, Shanghai 200062, China) |
| Abstract: |
| Objective: To probe into the value of biomarkers for kidney injury in evaluating calcineurin inhibitors(CNI)-associated
kidney injury. Methods: The rat model of adriamycin nephrotic syndrome was constructed and randomly divided into the blank control
group, hormone control group, hormone + cyclosporin (CsA) group and hormone + tacrolimus ( FK506) group. The levels of
biomarkers for kidney injury such as neutrophil gelatinase-associated lipid transport protein (NGAL), kidney injury molecule-1 (KIM-1),
interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), and kidney histopathologic
changes were statistically analyzed in the blood and urine of the four groups of rats at different time points (7, 14, and 21 d). Results:
There was no obvious injury in kidney pathology in the early stage. Kidney injury was fund in the middle stage of CNI treatment, which
worsened with the prolongation of treatment, and the injury was more severe in the hormone+CsA group than that in the hormone+FK506
group, the difference was statistically significant (P<0. 05). There were changes in NGAL, TNF-α and IL-18 in the early and middle
stages of CNI treatment, and changes in TGF-β in the late stage of CNI treatment, the differences were statistically significant compared
with hormone control group (P<0. 05). The levels of NGAL in hormone +CsA group was positively correlated with pathological score of
kidney tubulointerstitial injury (P <0. 05). Conclusion: NGAL, TNF-α and IL-18 are sensitive indicators for evaluating early and
middle CNI-related kidney injury, and TGF-β has better early warning value for late CNI-related kidney injury. The level of NGAL has
a better correlation with the pathological score of CsA-related kidney injury. |
| Key words: biomarkers of kidney injury cyclosporin tacrolimus kidney injury |
