Cheng Shi, Lu Wei, Xu Jiarui, Yu Yong, Fang Yi, Tan Xiao, Chen Ruizhen, Shen Bo, Ding Xiaoqiang, Xie Yeqing
Department of Nephrology, Zhongshan Hospital, Fudan University, No.180, Fenglin Road, Xuhui District, Shanghai, 200032, China.
Shanghai Key Laboratory of Kidney Disease and Dialysis, Shanghai, 200032, China.
BMC Nephrol. 2025 Jul 1;26(1):327. doi: 10.1186/s12882-025-04203-2.
Uremic cardiomyopathy (UCM) remains the leading cause of cardiovascular mortality in patients with end-stage renal disease (ESRD). Experimental animal models serve as essential tools for elucidating the potential mechanism underlying UCM. However, experimental UCM models are often challenged by inter-individual variability and inconsistent success rates. Reliable phenotypes are not guaranteed by current animal models of UCM. In this study, Tei index from echocardiography was investigated for its potential value in construction of murine UCM model based on 5/6 nephrectomy (Nx).
Comprehensive echocardiographic assessment, measurement of blood pressure and serum creatinine, histological analysis, and quantitative polymerase chain reaction (qPCR) were performed to reveal the relationship between Tei index and construction of UCM model.
The Tei index was significantly elevated in Nx mice despite preserved cardiac function and structural integrity at 8 weeks post-nephrectomy. A longitudinal follow-up to the 12 week revealed that the Nx mice with higher Tei index (Nx HT) presented distinct features of hemodynamic remodeling, left ventricular hypertrophy and diastolic dysfunction. Furthermore, pronounced myocardial hypertrophy and extensive myocardial interstitial fibrosis were confirmed in the Nx HT group.
This study validates the Tei index as a sensitive and non-invasive parameter for the early evaluation and prediction of UCM murine model induced by 5/6 nephrectomy.
尿毒症心肌病(UCM)仍然是终末期肾病(ESRD)患者心血管死亡的主要原因。实验动物模型是阐明UCM潜在机制的重要工具。然而,实验性UCM模型常常受到个体间差异和成功率不一致的挑战。目前的UCM动物模型无法保证可靠的表型。在本研究中,基于超声心动图的Tei指数在基于5/6肾切除术(Nx)构建小鼠UCM模型中的潜在价值进行了研究。
进行全面的超声心动图评估、血压和血清肌酐测量、组织学分析以及定量聚合酶链反应(qPCR),以揭示Tei指数与UCM模型构建之间的关系。
尽管肾切除术后8周心脏功能和结构完整性得以保留,但Nx小鼠的Tei指数显著升高。对12周的纵向随访显示,Tei指数较高的Nx小鼠(Nx HT)表现出明显的血流动力学重塑、左心室肥厚和舒张功能障碍特征。此外,Nx HT组证实有明显的心肌肥厚和广泛的心肌间质纤维化。
本研究验证了Tei指数作为5/6肾切除诱导的UCM小鼠模型早期评估和预测的敏感且非侵入性参数。