曲尼司特治疗通过抑制肥大细胞浸润预防大鼠慢性放射性结肠炎。

Tranilast Treatment Prevents Chronic Radiation-Induced Colitis in Rats by Inhibiting Mast Cell Infiltration.

作者信息

Seo Kyung Jin, Alam Mohammad Rizwan, Abdul-Ghafar Jamshid, Kim Sang Woo, Kim Hyung Keun, Choi Hyun Ho, Sin Seung Ho, Lee Hae Kyung, Chae Hiun Suk

机构信息

Department of Hospital Pathology, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea,

Department of Hospital Pathology, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

出版信息

Pharmacology. 2025;110(2):77-86. doi: 10.1159/000541003. Epub 2024 Aug 20.

DOI:10.1159/000541003

PMID:39163845

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11975317/

Abstract

INTRODUCTION

Mast cells are the principal cells involved in acute and chronic colitis due to radiation, known as radiation-induced colitis (RIC). In this study, we investigated whether pretreatment with tranilast, a mast cell inhibitor, could alleviate chronic RIC.

METHODS

A total of 23 Sprague-Dawley rats were randomly divided into three groups: control group (n = 5), radiation group (RG, n = 9), and tranilast-pretreated radiation group (TG, n = 9). The rats in the RG and the TG were irradiated in the pelvic area (1.5 cm from the anus) with a single dose of 20 Gy under general anesthesia. Tranilast (100 mg/kg) was administered intraperitoneally to the rats of the TG for 10 days, starting from the day of pelvic radiation. Ten weeks after radiation, the rats were euthanized. Rectal tissue samples were histologically evaluated for the total inflammation score (TIS) and mast cell count. The expression of MUC2, MUC5AC, and matrix metalloproteinase-9 (MMP-9) was also assessed immunohistochemically.

RESULTS

Both the TIS and specific components of TIS such as epithelial atypia, vascular sclerosis, and colitis cystica profunda (CCP) were significantly higher in the RG than in the TG (p = 0.02, 0.038, 0.025, and 0.01, respectively). Thein number of infiltrating mast cells was significantly higher in the RG than in the TG (median [range]: 20 [3-54] versus 6 [3-25], respectively; p = 0.034). Quantitatively, the number of MMP-9-positive cells was significantly higher in the RG (23.67 ± 19.00) than in the TG (10.25 ± 8.45) (mean ± standard deviation; p < 0.05). TIS and MMP-9 exhibited a strong association (correlation coefficient r = 0.56, p < 0.05). Immunohistochemically, the mucin-lake of CCP showed no staining for MUC5AC but was stained positive for MUC2.

CONCLUSION

Tranilast pretreatment of chronic RIC showed an anti-inflammatory effect associated with the reduction of mast cell infiltration and MMP-9 expression.

摘要

引言

肥大细胞是辐射所致急慢性结肠炎（即放射性结肠炎，RIC）中的主要参与细胞。在本研究中，我们调查了肥大细胞抑制剂曲尼司特预处理是否能缓解慢性RIC。

方法

总共23只Sprague-Dawley大鼠被随机分为三组：对照组（n = 5）、辐射组（RG，n = 9）和曲尼司特预处理辐射组（TG，n = 9）。RG组和TG组大鼠在全身麻醉下于盆腔区域（距肛门1.5 cm处）接受单次20 Gy的辐射。从盆腔辐射当天开始，给TG组大鼠腹腔注射曲尼司特（100 mg/kg），持续10天。辐射10周后，将大鼠安乐死。对直肠组织样本进行组织学评估，以确定总炎症评分（TIS）和肥大细胞计数。还通过免疫组织化学评估MUC2、MUC5AC和基质金属蛋白酶-9（MMP-9）的表达。

结果

RG组的TIS及其特定组成部分，如上皮异型增生、血管硬化和深部结肠炎囊肿（CCP），均显著高于TG组（p值分别为0.02、0.038、0.025和0.01）。RG组浸润性肥大细胞数量显著高于TG组（中位数[范围]：分别为20[3 - 54]和6[3 - 25]；p = 0.034）。定量分析显示，RG组MMP-9阳性细胞数量（23.67±19.00）显著高于TG组（10.25±8.45）（均值±标准差；p < 0.05）。TIS与MMP-9呈强相关性（相关系数r = 0.56，p < 0.05）。免疫组织化学结果显示，CCP的黏液湖对MUC5AC无染色，但对MUC2呈阳性染色。