课题组前期发现：纳米SiO2可激活JNK/c-Jun应激信号通路，引起参与调控心肌收缩功能的组织因子（TF）表达上调，但纳米SiO2对心肌收缩功能的影响及调控机制不清。本项目拟深入研究纳米SiO2对心肌收缩功能的影响及其分子机制。体内采用大鼠和斑马鱼模型研究纳米SiO2心肌损伤作用；小动物超声及磁共振分析心脏收缩功能的改变，免疫荧光检测心室收缩功能，通过心肌弹性成像、肌小节收缩长度和心肌收缩强度分析心肌收缩功能改变；原位杂交及免疫荧光检测心肌收缩蛋白表达及其与TF、PAR1共表达；qRT-PCR及Western blot检测JNK/c-Jun和TF/PAR1信号通路基因和蛋白表达水平，反向遗传学技术验证上述信号通路基因时空表达改变。体外采用心肌细胞构建JNK过表达和干扰体系，siRNA沉默TF，进一步验证JNK/c-Jun和TF/PAR1信号通路在纳米SiO2致心肌收缩功能障碍的调控机制。

Our previous study found that silica nanoparticles could activate the JNK/c-Jun signaling pathway and induce the upregulation of tissue factor (TF) which could impact the cardiac contraction function, but the mechanism was still not clear. This study is aimed to investigate the influence of silica nanoparticles on myocardial contraction function and its related mechanisms. The myocardial injury was dected in SD rats and zebrafish after exposed to silica nanoparticles. The cardiac contraction function in rats was anlazed by small animal doppler ultrasound and cardiac magnetic resonance. The immunofluorescence assay was performed to detect the ventricular contraction function. Myocardial elasticity imaging, sarcomere length contraction and the intensity of myocardial contraction were measured to analyze the effect of silica nanoparticles on myocardial contract function. The co-expression of tissue factor (TF), PAR1 and actin protein were detected by qRT-PCR and Western blot, and the JNK/c-Jun and TF/PAR1 signaling pathways were measured by immunofluorescence and in situ hybridization technique. Using the reverse genetics techniques, the invovled signaling pathways was further verified. Using lentiviruse for preparing JNK overexpression and knock-down cell culture system, and TF siRNA to analyze the changes in JNK/c-Jun and TF/PAR1 signaling pathways; and verified the regulatory mechanisms of JNK/c-Jun and TF/PAR1 signaling pathways in silica nanoparticles-induced myocardial contraction dysfunction.