心包纤维化和/或心包增厚是缩窄性心包炎（constrictive pericarditis，CP）患者血流动力学改变及临床症状的病理学基础，目前对其发生机制尚不清楚。我们的前期工作发现CP患者心包组织TGF-β1、P-Smad2/3和α-SMA表达量增加，心包间皮细胞(pericardial mesothelial cells, PMCs)向肌成纤维细胞转变。建立假说如下：TGF-β1/Smads通路活化诱导PMCs发生内皮-间质转化成为肌成纤维细胞引起胶原沉积及纤维化，IFN-γ可干预这一进程。本项目拟建立IFN-γ基因敲除大鼠CP模型，明确心包病变的影像学、病理学及分子生物学改变。分离IFN-γ基因敲除鼠及正常鼠PMCs，分别采用TGF-β1、Smad7过表达及IFN-γ干预，从细胞学水平明确IFN-γ阻断TGF-β1/Smads通路的机制。研究结果为临床治疗CP提供了重要的理论依据。

Pericardial fibrosis and/or thickness is the pathological basis of hemodynamic changes and clinical manifestations in patients with constrictive pericarditis(CP). However, the mechanism of pericardial fibrosis remains unclear. In the series of works in preliminary stage, we found the expression of TGF-β1, P-Smad2/3 and α-SMA in CP pericardia were increased, in addition to the pericardial mesothelial cells (PMCs) underwent epithelial-to-mesenchymal transition adapt to myofibroblast. Therefore, we presumed the main reason for pericardial fibrosis lies in here, that TGF-β1/Smads pathway induced PMCs differentiated to myofibrocyte, and caused pericardial fibrosis, IFN-γ could block the pathological development of CP by interrupting the pathway. According to the above hypothesis, we developed the IFN-γ-knock-out (IFN-γ-KO) rats model of CP and confirmed the echocardiographic changes and molecular mechanism of pericardial fibrosis. We isolated and cultured the PMCs of IFN-γ-KO rats and normal rats, and treated with TGF-β1, IFN-γ and over-expression of Smad7 to investigate the role TGF-β1/Smads signal pathway in the progression of fibrosis. This research will not only clarifies the mechanism of CP, but also provides the theoretical and experimental basis for the clinical treatment of CP.