Silica nanoparticles induce JNK-mediated inflammation and myocardial contractile dysfunction

JOURNAL OF HAZARDOUS MATERIALS

卷:391

Article

Feng, Lin^1,2  Ning, Ruihong^1,2  Liu, Jiangyan^1,2  Liang, Shuang^1,2  Xu, Qing⁴  Liu, Ying^5,6  Liu, Wei³  Duan, Junchao^1,2  Sun, Zhiwei^1,2 

[1] Capital Med Univ, Sch Publ Hlth, Dept Toxicol & Sanit Chem, Beijing 100069, Peoples R China

[2] Capital Med Univ, Beijing Key Lab Environm Toxicol, Beijing 100069, Peoples R China

[3] Capital Med Univ, Cardiol Dept, Affiliated Beijing Anzhen Hosp, Beijing 100029, Peoples R China

[4] Capital Med Univ, Core Facil Ctr, Core Facil Electrophysiol, Beijing 100069, Peoples R China

[5] Natl Ctr Nanosci & Technol China, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China

[6] Natl Ctr Nanosci & Technol China, CAS Ctr Excellence Nanosci, Beijing 100190, Peoples R China

关键词: Silica nanoparticles;    Subacute exposure;    Myocardial contractile dysfunction;    Inflammation;    JNK/TF/PAR1 pathway;   

DOI  :  10.1016/j.jhazmat.2020.122206

来源: Elsevier

【 摘 要 】

Increasing environmental exposure to silica nanoparticles (SiNPs) and limited cardiotoxicity studies posed a challenge for the safety evaluation and management of these materials. This study aimed to explore the adverse effects and underlying mechanisms of subacute exposure to SiNPs on cardiac function in rats. Results from echocardiographic, ultrastructural and histopathological analysis found that SiNPs induced cardiac contractile dysfunction, accompanied by incomplete myocardial structures, disordered sarcomere segments, interstitial edema and myocyte apoptosis in heart. Levels of myocardial enzymes and inflammatory factors were markedly increased in both serum and heart tissue, accompanied by elevated levels of oxidative damage occurred in the hearts of SiNPs-treated rats. SiNPs significantly upregulated the expressions of inflammation and contraction-related proteins, including JNK, p-JNK, c-Jun, TF and PAR1. Lentivirus transfection of JNK shRNA showed the low-expression of JNK-facilitated F-actin and inhibited TF in the SiNPs-treated cardiomyocytes. Moreover, SiNPs activated the mRNA and protein levels of JNK/TF/PAR1 pathway, and these effects were significantly dampened after JNK knock down. Our results demonstrate that SiNPs trigger myocardial contractile dysfunction via JNK/TF/PAR1 signaling pathway.

【 授权许可】

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