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目的 探究三重基序蛋白21(TRIM21)在顺铂诱导的急性肾损伤(Cis-AKI)小鼠模型中不同时间点的表达及和病理评分的相关性。方法 通过给小鼠腹腔注射顺铂(20 mg/kg)诱导急性肾损伤(AKI)模型，分别在12、24、48、72 h收集小鼠外周血清。同时记录小鼠体质量与肾脏质量。检测血清中血肌酐(SCr)和尿素氮(BUN)的动态变化。Western blot检测TRIM21蛋白及内质网应激(ERS)蛋白GRP78、GRP94、P-elf2α、CHOP的表达。HE染色观察肾组织病理并和TRIM21的蛋白表达作不同时间点的相关性分析。结果 与对照组相比，Cis-AKI小鼠肾体比在48、72 h均升高(P<0.01),SCr和BUN在48、72 h均升高(P<0.01)。HE染色显示，与对照组相比，Cis-AKI小鼠肾脏病理评分在12、24 h均有一定增加(P<0.000 1),同时，TRIM21蛋白的表达在24 h增加(P<0.01)。与对照组相比，Cis-AKI小鼠肾脏病理评分在48 h增加(P<0.000 1),且TRIM21、CHOP、GRP78的蛋白表达在48 h均上调(P<0.05)。与对照组相比，Cis-AKI小鼠肾脏病理评分在72 h增加(P<0.000 1),同时，TRIM21、GRP94、P-elf2α蛋白的表达在72 h均上调(P<0.05)。相关性分析结果显示，不同时间点TRIM21蛋白的表达与不同时间点HE病理评分之间存在正相关性(P<0.000 1)。结论 在不同时间点下，TRIM21可能通过影响ERS参与Cis-AKI的病理进展，其与肾脏病理评分呈现正相关，有望成为潜在的早期诊断标志物与干预靶点。
Abstract：Objective To investigate the expression of triple motif protein 21(TRIM21) at different time points in Cisplatin induced acute kidney injury(Cis-AKI) mouse model and its correlation with pathological score.Methods Acute kidney injury(AKI) model was induced by intraperitoneal injection of cisplatin(20 mg/kg).Peripheral blood serum was collected at 12,24,48 and 72 h,respectively.Body weight and kidney mass were also recorded.The dynamic changes of serum creatinine(SCr) and urea nitrogen(BUN) were detected.The expressions of TRIM21 protein and endoplasmic reticulum stress(ERS) proteins GRP78,GRP94,P-elf2α and CHOP were detected by Western blot.HE staining was used to observe the pathology of renal tissue and analyze the correlation between the expression of TRIM21 protein at different time points.Results Compared with the control group,the renal body ratio of Cis-AKI mice significantly increased at 48 h and 72 h(P <0.01).SCr and BUN of Cis-AKI mice significantly increased at 48 h and 72 h compared with control group(P <0.01).HE staining showed that compared with the control group,the renal pathological scores of Cis-AKI mice increased at 12 and 24 h(P <0.000 1).At the same time,the expression of TRIM21 protein significantly increased at 24 h(P <0.01).Compared with the control group,the renal pathological score of Cis-AKI mice significantly increased at 48 h(P <0.000 1),and the protein expression of TRIM21,CHOP and GRP78 was significantly up-regulated at 48 h(P <0.05).Compared with the control group,the renal pathological score of Cis-AKI mice significantly increased at 72h(P <0.000 1),and the expression of TRIM21,GRP94 and P-elf2α proteins was significantly up-regulated at 72h(P <0.05).The results of correlation analysis showed that the expression of TRIM21 protein at different time points was positively correlated with the HE pathological scores at different time points(P <0.000 1).Conclusion At different time points,TRIM21 may participate in the pathological progression of Cis-AKI by affecting ERS,and it is positively correlated with renal pathological scores,which is expected to become a potential early diagnostic marker and intervention target.
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2025.11.003
中图分类号:R965
引用信息:
[1]孙晴晴,倪蕾,魏伟,等.TRIM21与顺铂诱导小鼠急性肾损伤的相关性[J].安徽医科大学学报,2025,60(11):2005-2010.DOI:10.19405/j.cnki.issn1000-1492.2025.11.003.
基金信息:
安徽省重点研究与开发计划(编号:202307020003)~~