曲尼司特治疗可通过抑制肥大细胞浸润来预防慢性辐射诱导的大鼠结肠炎。

IF 2.9 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pharmacology Pub Date : 2024-08-20 DOI:10.1159/000541003
Kyung Jin Seo, Mohammad Rizwan Alam, Jamshid Abdul-Ghafar, Sang Woo Kim, Hyung Keun Kim, Hyun Ho Choi, Seung Ho Sin, Hae Kyung Lee, Hiun Suk Chae
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引用次数: 0

摘要

导言肥大细胞是导致辐射引起的急性和慢性结肠炎(RIC)的主要细胞。在此,我们研究了预处理肥大细胞抑制剂氨曲司特能否缓解慢性 RIC:方法:将23只Sprague Dawley(SD)大鼠随机分为三组:对照组(n=5,C)、辐照组(n=9,RG)和经氨替拉斯特预处理的辐照组(n=9,TG)。RG 和 TG 组大鼠在全身麻醉的情况下,在骨盆区域(距肛门 1.5 厘米处)接受单次剂量为 20 Gray 的照射。自盆腔照射之日起,连续 10 天为 TG 组小鼠腹腔注射曲尼司特(100 毫克/千克)。照射十周后,大鼠被安乐死。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。还对 MUC2、MUC5AC 和基质金属蛋白酶 9(MMP9)的表达进行了免疫组化评估:结果:RG的TIS和TIS的某些成分、上皮不典型性、血管硬化和深部结肠炎(CCP)均明显高于TG(P分别为0.02、0.038、0.025、0.01)。浸润肥大细胞的数量在 RG 中明显高于 TG(分别为 20,3-54 和 6,3-25,P=0.034)。从数量上看,RG 中 MMP9 阳性细胞的数量(23.67±19.00)明显高于 TG(10.25±8.45)(P<0.05)。TIS和MMP9表现出很强的相关性(相关系数r=0.56,P<0.05)。免疫组化显示,CCP的粘蛋白湖没有MUC5AX染色,但MUC2阳性:结论:曲尼司特在 RIC 中的预处理显示出对 RIC 的抗炎作用,这与肥大细胞浸润和 MMP9 表达的减少有关。
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Tranilast Treatment Prevents Chronic Radiation-Induced Colitis in Rats by Inhibiting Mast Cell Infiltration.

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.

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来源期刊
Pharmacology
Pharmacology 医学-药学
CiteScore
5.60
自引率
0.00%
发文量
52
审稿时长
6-12 weeks
期刊介绍: ''Pharmacology'' is an international forum to present and discuss current perspectives in drug research. The journal communicates research in basic and clinical pharmacology and related fields. It covers biochemical pharmacology, molecular pharmacology, immunopharmacology, drug metabolism, pharmacogenetics, analytical toxicology, neuropsychopharmacology, pharmacokinetics and clinical pharmacology. In addition to original papers and short communications of investigative findings and pharmacological profiles the journal contains reviews, comments and perspective notes; research communications of novel therapeutic agents are encouraged.
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