运动调控B细胞活化保护心肌梗死及其机制

Acute myocardial infarction (AMI) is one of the leading life-threatening diseases. The immune system becomes activated in response to AMI. The previous studies by us and other groups indicated that B-cells depletion in mice limited infarct expansion and fibrosis in non-infarcted myocardium and alleviated left ventricular dilatation and systolic dysfunction post-myocardial infarction, which means B-cells were involved in the process of AMI. Beside that, our previous work has uncovered that exercise training could reduce the infarct size and preserve cardiac function post-myocardial infarction. The innate antibodies production in these treadmill exercise trained mice was downregulated compared to control mice, demonstrated that exercise could regulate B-cells activation in mice. However, the molecular mechanism of exercise in regulating B-cells activation and B-cells underlying the protect mechanism of exercise training during the AMI is unclear. In this project, we will investigate the regulation mechanism of exercise trained B-cells underlying the protective effect of exercise in AMI. In addition, we will reveal the mechanism of exercise in regulating cardiac infiltrated B-cells protective function in AMI mouse model. We hope to clarify the new mechanism of B-cells in the treatment of heart diseases through this study and provide new concept for immunotherapy in associated diseases.

急性心肌梗死严重危害人类健康，在其发病过程中免疫细胞所发挥的调节作用越来越受到广泛关注。我们及其他研究组的实验研究均发现，缺失B细胞的小鼠心肌梗死手术后梗死区面积以及心脏纤维化程度均显著减少，心功能明显改善，表明B细胞参与心肌梗死的发病进程。此外我们的预实验发现运动训练可以保护小鼠心肌梗死后的心功能，且运动训练小鼠血清中本底抗体分泌显著发生改变，表明运动训练对小鼠B细胞活化及功能发挥具有一定调控作用。但运动调控的B细胞活化在运动保护心肌梗死中的作用及其机制尚不清楚。在本项目中，我们拟通过构建运动保护心肌梗死小鼠模型，阐明运动调控B细胞活化在保护心肌梗死中的功能，同时综合运用活细胞动态成像技术以及传统生化手段，进一步揭示运动调控B细胞活化介导心肌梗死保护效应的机制。希望通过对B细胞在运动保护心脏作用中的功能探究揭示B细胞在心脏疾病治疗中的新机制，为相关疾病的免疫治疗提供新思路。

急性心肌梗死严重危害人类健康，在其发病过程中免疫细胞所发挥的调节作用越来越受到广泛关注。我们及其他研究组的实验研究均发现，缺失B细胞的小鼠心肌梗死手术后梗死区面积以及心脏纤维化程度均显著减少，心功能明显改善，表明B细胞参与心肌梗死的发病进程。此外我们的预实验发现运动训练可以保护小鼠心肌梗死后的心功能，且运动训练小鼠血清中本底抗体分泌显著发生改变，表明运动训练对小鼠B细胞活化及功能发挥具有一定调控作用。但运动调控的B细胞活化在运动保护心肌梗死中的作用及其机制尚不清楚。在本项目中，我们通过构建运动保护心肌梗死小鼠模型，阐明运动调控B细胞活化在保护心肌梗死中的功能，同时综合运用活细胞动态成像技术以及传统生化手段，进一步揭示运动调控B细胞活化介导心肌梗死保护效应的机制。通过对B细胞在运动保护心脏作用中的功能探究，我们揭示了B细胞在心脏疾病治疗中的新机制，为相关疾病的免疫治疗提供新思路。