Atorvastatin, etanercept and the nephrogenic cardiac sympathetic remodeling in chronic renal failure rats  

作　　者：Jing-Yue XU Zheng-Kai XUE Ya-Ru ZHANG Xing LIU Xue ZHANG Xi YANG Tong LIU Kang-Yin CHEN 

机构地区：[1]Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease,Department of Cardiology,Tianjin Institute of Cardiology,the Second Hospital of Tianjin Medical University,Tianjin,China

出　　处：《Journal of Geriatric Cardiology》2024年第4期443-457,共15页老年心脏病学杂志（英文版）

基　　金：supported by the Key Project of Tianjin Natural Science Foundation (No.21JCZDJC01080);the Tianjin Key Medical Discipline (Specialty) (TJYXZDX K-029A);the Academic Backbone of “Clinical Talent Training and Climbing Plan” of Tianjin Medical University and the Tianjin Health Research Project;Science and Technology Development Fund of Nanjing Medical University (NMUB20210180)。

摘　　要：BACKGROUND Chronic renal failure(CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia(VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this process.METHODS A total of 48 rats were randomly divided into sham operation group(Sham group), CRF group, CRF + atorvastatin group(CRF + statin group), and CRF + etanercept group(CRF + rhTNFR-Fcgroup). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43(GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha(TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent assay.RESULTS Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay,immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + rhTNFR-Fcgroup.CONCLUSIONS In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept could downregulate the expression of TNF-α or

关 键 词：REMODELING CARDIAC inhibited 

分 类 号：R692.5[医药卫生—泌尿科学]