中国血液净化

中国血液净化 ›› 2025, Vol. 24 ›› Issue (10): 818-822.doi: 10.3969/j.issn.1671-4091.2025.10.006

• 临床研究 • 上一篇    下一篇

口服活性炭吸附剂改善维持性血液透析患者肠上皮细胞屏障的破坏

魏 萌    魏丽敏   赵 雪     王 敬    蒋红利    梁珊珊   

  1. 710061 西安，西安交通大学第一附属医院1重症肾脏病・血液净化科 3输血科
    723000 汉中，2汉中市中心医院肾脏内科
  • 收稿日期:2025-01-03 修回日期:2025-07-21 出版日期:2025-10-12 发布日期:2025-10-12
  • 通讯作者: 梁珊珊 E-mail:lss2056@163.com
  • 基金资助:
    陕西省重点研发计划一般项目(2023-YBSF-239)

Oral medicinal charcoal tablets alleviates intestinal epithelial barrier damage in maintenance hemodialysis patients

WEI Meng, WEI Li-min, ZHAO Xue, WANG Jing, JIANG Hong-li, LIANG Shan-shan   

  1. Department of Critical Care Nephrology and Blood Purification, 3Department of blood transfusion, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China; 2Department of Nephrology, Hanzhong Central Hospital, Hanzhong 723000, China
  • Received:2025-01-03 Revised:2025-07-21 Online:2025-10-12 Published:2025-10-12
  • Contact: 710061 西安，西安交通大学第一附属医院3输血科 E-mail:lss2056@163.com
  • Supported by:

摘要： 目的 探讨维持性血液透析患者口服活性炭吸附剂后对肠上皮屏障的影响。 方法 选择2015年12月—2016年3月汉中市中心医院肾脏内科维持性血液透析患者为研究对象，随机分为血液透析(hemodialysis，HD)组和口服药用炭片(medicinal charcoal tablets,MCT)组(3片/次，3次/d，连服3个月)，同期选择门诊健康体检者作为对照组(Control组)。使用Caco2细胞构建单层细胞模型，分别给予浓度为10%的不同分组混合血清进行干预，使用电阻仪检测肠上皮细胞Caco2跨膜电阻(transepithelial electrical resistance,TEER)，噻唑蓝(Methylthialazole Tetrazolium，MTT)比色法检测细胞生长增殖率，Western blot法检测紧密连接密封蛋白claudin-1、闭合蛋白occludin和膜外周蛋白(zonula occludens-1,ZO-1)水平。 结果 HD组、MCT组、对照组各入选9例研究对象留取血清，每3例制备成混合血清用于后续干预肠上皮细胞。与Control组相比，HD组血清对肠上皮细胞分别作用24 h和48 h后，TEER降低(24 h：t=11.436,P=0.004；48h:t=11.587,P=0.001)，细胞活力和增殖能力有明显抑制(24 h:t=10.701，P=0.007；48 h:t=-5.295，P=0.002)，且与作用时间呈正比(HD组干预24 h与48 h相比,TEER t=17.206，P＜0.001；细胞活力：t=10.701，P＜0.001)；HD组紧密连接(tight junction,TJ)相关蛋白claudin-1(t=17.962，P=0.003)，occludin(t=6.824，P=0.021)，ZO-1(t=8.070，P=0.015)的表达降低。与Control组相比，MCT 组血清作用不同时间后，TEER降低(24h：t=-7.420，P=0.001；48h：t=-6.969，P=0.004)，细胞增值活力轻度下降(24 h：t=17.746，P=0.039；48 h：t=-2.911，P=0.042)，TJ蛋白claudin-1(t=6.346，P=0.032)及ZO-1(t=8.356，P=0.043)蛋白表达降低，occludin表达量变化未达统计学差异(t=3.897，P=0.060)。 结论  尿毒症时肠上皮屏障功能受损，口服药用炭片可减轻尿毒症引起的肠上皮TJ结构的破坏。

关键词: 尿毒症, 肠上皮屏障, 活性炭, 吸附剂, 紧密连接

Abstract: Objective  To investigate the effect of oral medicinal charcoal tablets on the structure of intestinal epithelial barrier in maintenance hemodialysis patients.  Methods  Patients undergoing maintenance hemodialysis in the Nephrology Department of Hanzhong Central Hospital from December 2015 to March 2016 were selected as subjects and randomly assigned to a hemodialysis (HD) group and a medicinal charcoal tablets (MCT) group (3 tablets/time, 3 times/day for 3 consecutive months). Healthy individuals from outpatient physical examinations during the same period were selected as the control group (Control group). A monolayer cell model was constructed using Caco-2 cells. The cells were cultured with 10% mixed serum from different groups for intervention. Transepithelial electrical resistance (TEER) of Caco-2 intestinal epithelial cells was measured using a resistance meter. Cell growth and proliferation rates were assessed using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) colorimetric assay. The expression levels of tight junction proteins claudin-1, occludin, and zonula occludens-1 (ZO-1) were detected by Western blot.  Results  Serum samples were collected from 9 subjects each in the HD, MCT, and Control groups. Every 3 serum samples were pooled to create mixed serum for subsequent intervention on intestinal epithelial cells. Compared to the Control group, serum from the HD group significantly reduced TEER of intestinal epithelial Caco-2 cells after 24 h and 48 h of intervention (24 h: t =11.436, P=0.004; 48 h: t =11.587, P =0.001), inhibited cell viability and proliferation (24 h: t =10.701, P =0.007; 48 h: t =-5.295, P =0.002), and these effects were time-dependent (comparison between 24 h and 48 h in the HD group: TEER t =17.206, P<0.001; cell viability: t =10.701, P< 0.001). The expression levels of tight junction (TJ) proteins claudin-1 (t =17.962, P =0.003), occludin (t =6.824, P = 0.021), and ZO-1 (t =8.070, P =0.015) were decreased in the HD group. Compared to the Control group, serum from the MCT group also reduced TEER after different intervention times (24 h: t =-7.420, P =0.001; 48 h: t =-6.969, P =0.004) and mildly decreased cell proliferation viability (24 h:t=17.746, P=0.039; 48 h:t=-2.911, P =0.042). The expression levels of claudin-1 (t =6.346, P =0.032) and ZO-1 (t =8.356, P =0.043) were reduced, while the change in occludin expression did not reach statistical significance (t =3.897, P =0.060). Conclusions Uremia impairs intestinal epithelial barrier function. Oral medicinal charcoal tablets can mitigate the damage to intestinal epithelial tight junction structures caused by uremia.

Key words: Uremia, Intestinal epithelial barrier, Oral activated charcoal, Adsorbent, Tight junction

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