| 摘要: |
| [目的] 探讨苦参注射液（以下简称KS）是否通过活性氧（ROS）/PTEN 诱导激酶 1（PINK1）-帕金森病蛋白（Parkin）介导的线粒体自噬途径保护上皮屏障，从而干预放射性食管炎（RE）损伤。[方法] 研究采用随机对照双盲试验，纳入70例接受根治性胸部放疗（≥50 Gy）的食管癌/肺癌患者，随机分为 KS 组（静脉滴注KS 20 mL）和RE组（等量生理盐水静脉滴注），通过胃镜于食管炎症处取材，液氮速冻后保存。采用视觉模拟评分（VAS）、放射治疗肿瘤协作组（RTOG）吞咽困难分级评估临床疗效，记录黏膜愈合时间；对标本进行苏木精-伊红（HE）染色观察；透射电子显微镜检查组织形态，二氢乙锭（DHE）荧光探针检测ROS水平，蛋白质免疫印迹分析检测相关蛋白表达。[结果] 与RE组比较，KS组VAS评分降低，吞咽困难分级降低，且黏膜愈合时间缩短（P<0.001）；RE组透明化、血管扩张和炎性细胞增加，KS组这些病理改变明显改善；与RE组比较，KS组PINK1、Parkin蛋白表达和微管相关蛋白1轻链3（LC3）-Ⅱ/LC3-Ⅰ表达增加（P<0.001），p62蛋白降低（P<0.001）。此外，RE组线粒体表现出肿胀、结构模糊、嵴消失或碎裂、基质电子密度降低和空泡化，KS组线粒体肿胀和结构模糊不明显；与RE组比较，KS组ROS水平降低（P<0.001），闭锁小带蛋白-1（ZO-1）和闭锁蛋白（Occludin）增加（P<0.001）；ROS水平与ZO-1表达呈显著负相关（r=-0.82，P=0.001），PINK1表达与线粒体自噬体数量呈强正相关（r=0.78，P=0.001）。[结论] KS对放射性食管炎的保护作用与其降低ROS水平及激活PINK1-Parkin通路密切相关，提示其可能存在一种“通过清除毒性ROS来增强线粒体自噬、重建上皮屏障”的潜在级联机制，为RE防治提供了新的实验证据和思路。 |
| 关键词: 苦参注射液 活性氧/PTEN诱导激酶1-帕金森病蛋白 放射性食管炎 线粒体自噬 |
| DOI：10.11656/j.issn.1673-9043.2026.09.05 |
| 分类号:R571 |
| 基金项目:河北省2025年度中医药类科学研究课题项目（2025188）。 |
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| Clinical observation of Kushen Injection for radiation-induced esophagitis injury |
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ZHENG Xiao1, LI Guijun1, WANG Yuanyuan1, ZHANG Jianhua2, LI Jingmin1
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1.Third Department of Oncology, Handan Hospital of Integrated Traditional Chinese & Western Medicine, Handan 056002, China;2.Sixth Department of Oncology, Handan Hospital of Integrated Traditional Chinese & Western Medicine, Handan 056002, China
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| Abstract: |
| [Objective] To investigate whether Kushen Injection（KS） protects the epithelial barrier via the reactive oxygen species（ROS）/PTEN-induced kinase 1（PINK1）-Parkin-mediated mitophagy pathway，thereby intervening in radiation esophagitis（RE） injury. [Methods] This randomized，double-blind，controlled trial enrolled 70 patients with esophageal/lung cancer receiving radical thoracic radiotherapy（≥50 Gy）. Patients were randomly divided into the KS group（intravenous infusion of 20 mL Kushen Injection） and the RE group（intravenous infusion of an equal volume of normal saline）. Esophageal inflammatory tissues were sampled via gastroscopy，snap-frozen in liquid nitrogen，and stored. Clinical efficacy was evaluated using the Visual Analog Scale（VAS） pain score and the Radiation Therapy Oncology Group（RTOG） dysphagia grade，and mucosal healing time was recorded. Specimens underwent HE staining；tissue morphology was examined by transmission electron microscopy；ROS levels were detected using a dihydroethidium（DHE） fluorescent probe；and related protein expression was analyzed by Western blotting. [Results] Compared with the RE group，the KS group showed decreased VAS scores，reduced dysphagia grades，and shortened mucosal healing time（P<0.001）. The RE group displayed hyalinization，vascular dilation，and increased inflammatory cells，whereas these pathological changes were markedly improved in the KS group. Compared with the RE group，the KS group exhibited increased protein expression of PINK1 and Parkin，an increased microtubule-associated protein 1 light chain 3（LC3）-II/LC3-I ratio（P<0.001），and decreased p62 protein（P<0.001）. Moreover，mitochondria in the RE group showed swelling，blurred structure，loss or fragmentation of cristae，decreased matrix electron density，and vacuolization，while mitochondrial swelling and structural blurring were not obvious in the KS group. Compared with the RE group，the KS group had reduced ROS levels（P<0.001） and increased zonula occludens-1（ZO-1） and Occludin expression（P<0.001）. ROS level was significantly negatively correlated with ZO-1 expression（r=-0.82，P=0.001），and PINK1 expression was strongly positively correlated with the number of mitophagosomes（r=0.78，P=0.001）. [Conclusion] The protective effect of Kushen Injection（KI） on radiation esophagitis（RE） is closely associated with its role in reducing reactive oxygen species（ROS） levels and activating the PINK1-Parkin pathway，suggesting that it may have a potential cascade mechanism of “enhancing mitophagy and rebuilding the epithelial barrier by eliminating toxic ROS”，which provides new experimental evidence and ideas for the prevention and treatment of RE. |
| Key words: Kushen Injection ROS/PINK1-Parkin radiation-induced esophagitis mitophagy |
