Zhang Miao-Xin, Wu Chi, Feng Xin-Xia, Tian Wei, Zhao Ning-Hui, Lu Pan-Pan, Ding Qiang, Liu Mei
Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
World J Gastroenterol. 2025 Jun 21;31(23):106949. doi: 10.3748/wjg.v31.i23.106949.
The role of NLR family pyrin domain containing 3 (NLRP3) in post-endoscopic submucosal dissection (ESD) esophageal stricture remains incompletely understood. The effect of celastrol (CEL) on the prevention of esophageal strictures has not yet been investigated.
To explore the effect of CEL on the prevention of esophageal stricture in rats.
NLRP3, interleukin (IL)-1β, and IL-18 mRNA levels were measured in patients' tissues after esophageal ESD. NLRP3 expression in esophageal fibroblasts was determined using immunohistochemistry and immunofluorescence staining. Lentiviral transfection was used to induce NLRP3 overexpression and thioredoxin reductase 1 (TXNRD1) silencing. The CCK8 assay was used to determine the optimal CEL concentration. Reactive oxygen species (ROS) generation was detected fluorescence and flow cytometry. Masson's trichrome staining and barium esophagography were performed to assess collagen deposition and esophageal stenosis.
The mRNA levels of NLRP3 and IL-1β were higher in human tissues from the ESD resection bed than in normal esophageal mucosa. NLRP3 overexpression in primary rat esophageal fibroblasts led to high collagen 1 expression. Thus, NLRP3 participated in esophageal inflammation and tissue repair after ESD. Comparable to prednisolone, CEL significantly inhibited NLRP3 activation and , and esophageal strictures were markedly alleviated. Mechanistically, CEL upregulated TXNRD1 expression and reduced ROS production, thereby inhibiting NLRP3 expression. This effect was reversed by TXNRD1 silencing. Furthermore, TXNRD1 interacted with NLRP3 and promoted its ubiquitination.
CEL is a promising alternative therapeutic agent for the prevention of post-ESD esophageal strictures.
含NLR家族pyrin结构域蛋白3（NLRP3）在内镜下黏膜下剥离术（ESD）后食管狭窄中的作用仍未完全明确。雷公藤红素（CEL）对预防食管狭窄的作用尚未得到研究。
探讨CEL对大鼠食管狭窄的预防作用。
检测食管ESD术后患者组织中NLRP3、白细胞介素（IL）-1β和IL-18的mRNA水平。采用免疫组织化学和免疫荧光染色法测定食管成纤维细胞中NLRP3的表达。利用慢病毒转染诱导NLRP3过表达和硫氧还蛋白还原酶1（TXNRD1）沉默。采用CCK8法测定CEL的最佳浓度。通过荧光和流式细胞术检测活性氧（ROS）的生成。进行Masson三色染色和食管钡餐造影以评估胶原沉积和食管狭窄情况。
ESD切除床的人体组织中NLRP3和IL-1β的mRNA水平高于正常食管黏膜。原代大鼠食管成纤维细胞中NLRP3过表达导致胶原蛋白1表达升高。因此，NLRP3参与了ESD后的食管炎症和组织修复。与泼尼松龙类似，CEL显著抑制NLRP3的激活，食管狭窄明显减轻。机制上，CEL上调TXNRD1表达并减少ROS生成，从而抑制NLRP3表达。TXNRD1沉默可逆转这一作用。此外，TXNRD1与NLRP3相互作用并促进其泛素化。
CEL是预防ESD后食管狭窄的一种有前景的替代治疗药物。
