食管支架置入是目前治疗良性狭窄的常用方法。食管支架可显著扩张狭窄食管、改善吞咽困难症状，但支架相关狭窄限制支架的长期通畅性，严重影响了患者的生活质量。因此，亟需能有效减少支架相关狭窄的方法和手段。研究发现功能性金纳米涂层支架可通过局部光热效应显著减少大鼠食管支架相关狭窄，但前期研究随访观察时间短，无法评估长期疗效。本课题组的前期预实验发现，局部光热治疗短期内可有效减少支架相关狭窄，延长随访观察时间发现，术后周支架段食管可见新生肉芽组织，可能机制为局部热处理后基底部残存的成纤维细胞活化增殖，因此我们预测抗成纤维细胞活化增殖联合局部光热效应可能更有效减少支架相关狭窄。EW7917是特异性TGF-β受体1抑制剂，可通过抑制TGF-β-Smad通路活性抑制成纤维细胞增殖和活性。本研究拟采用新型EW-7197载药金纳米颗粒涂层支架在大鼠模型中探究EW7917联合光热效应在支架相关狭窄的疗效和机制。

Benign esophageal stricture is a challenging clinical condition. Its most common symptom is dysphagia, which could result in weight loss and malnutrition thereby affecting the patient’s quality of life. Stent placement is commonly performed to treat benign esophageal stricture, particularly those who are refractory to balloon dilation. It could dilate the stricture and ameliorate the symptom of dysphagia thereby improving the patient’s quality of life. However, stent-related tissue hyperplasia has limited its wide spread use and therefore, it is clinically necessary to overcome this obstacle. Nanofuntionalized stent-mediated local heat treatment has been considered as a promising approach to prevent stent-related tissue hyperplasia, but the long-term outcomes are unclear. In our pilot study, we found that, GNP-mediated local heating can significantly reduce stent-related tissue hyperplasia during a 4-week follow-up, but new granulation tissues were observed at 8-week follow-up. This may be the pathological consequence of the activation and proliferation of the remaining myofibroblast located in the bottom of the granulation tissue after local heat treatment, and indicates that further treatment may be required to prevent stent-related tissue hyperplasia in the long-term. EW-7197, an activin-like kinase 5 inhibitor, has been shown to be able to effectively suppress stent-related tissue hyperplasia by inhibiting the activity of TGF-β-Smad pathway. In the present study, we aim to investigate if EW7197-loading AuNPs-coated stent-mediated combination treatment of EW-7197 and local heat treatment would be more effective in preventing stent-related tissue hyperplasia in a rat model. Through our current study, we may provide basis for a novel stent therapy to treat benign esophageal stricture.