Chen Yan, Chen Yi, Liu Wei-li, Zhou Tian-hua, Cai Jian-ting, Du Qing, Wang Liang-jing, Wu Jia-Guo, Si Jian-min
Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
J Gastroenterol Hepatol. 2009 May;24(5):912-9. doi: 10.1111/j.1440-1746.2008.05721.x. Epub 2009 Feb 9.
The aim of this study was to investigate whether rectal administration of muscovite can ameliorate colonic inflammation in a rat model of experimental colitis, and its possible mechanism.
Female Sprague-Dawley (SD) rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis were treated with rectal administration of muscovite or 5-aminosalicylic acid (5-ASA) daily for 14 days. The changes in body weight, macroscopic damage and histologic scores were subsequently evaluated. Gene expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), mucin2 (MUC2) and trefoil factor 3 (TFF3) in the colonic tissues was assessed by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) while protein levels of TNF-alpha and IL-1beta were detected by ELISA. Mucin2 expression in colonic mucosa was detected by immunohistochemistry. The capacity of muscovite to adsorb cytokines in vitro was determined by the changes in the amount of TNF-alpha, IL-1beta secreted by lipopolysaccharide (LPS)-stimulated THP-1 cells and IL-8 secreted by LPS-stimulated HT-29 cells.
Rectal administration of muscovite improved the loss of body weight, macroscopic and histologic scores of TNBS-induced colitis in a dose-dependent manner. Trinitrobenzene sulfonic acid-induced expression of TNF-alpha and IL-1beta was reduced by muscovite and 5-ASA treatment. Reduction of MUC2 expression in colitis rats was reversed by muscovite and 5-ASA treatment. However, the expression of TFF3 mRNA in colonic mucosa was not affected. In addition, we found muscovite inhibited the expression of TNF-alpha, IL-1beta secreted by THP-1 and IL-8 secreted by HT-29 cells in a dose-dependent manner.
Our study demonstrated for the first time that rectal administration of muscovite can ameliorate colonic inflammation of TNBS-induced colitis. Further confirmatory studies are needed to prove that muscovite might be a potential therapeutic agent for the treatment of ulcerative colitis.
本研究旨在探讨直肠给予白云母是否能改善实验性结肠炎大鼠模型的结肠炎症及其可能机制。
用三硝基苯磺酸（TNBS）诱导雌性斯普拉格-道利（SD）大鼠患结肠炎，每日直肠给予白云母或5-氨基水杨酸（5-ASA），持续14天。随后评估体重变化、大体损伤和组织学评分。通过半定量逆转录聚合酶链反应（RT-PCR）评估结肠组织中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、黏蛋白2（MUC2）和三叶因子3（TFF3）的基因表达，同时用酶联免疫吸附测定（ELISA）检测TNF-α和IL-1β的蛋白水平。通过免疫组织化学检测结肠黏膜中黏蛋白2的表达。通过脂多糖（LPS）刺激的THP-1细胞分泌的TNF-α、IL-1β量的变化以及LPS刺激的HT-29细胞分泌的IL-8量的变化来测定白云母在体外吸附细胞因子的能力。
直肠给予白云母以剂量依赖性方式改善了TNBS诱导的结肠炎大鼠的体重减轻、大体和组织学评分。白云母和5-ASA处理降低了TNBS诱导的TNF-α和IL-1β表达。白云母和5-ASA处理逆转了结肠炎大鼠中MUC2表达的降低。然而，结肠黏膜中TFF3 mRNA的表达未受影响。此外，我们发现白云母以剂量依赖性方式抑制THP-1分泌的TNF-α、IL-1β以及HT-29细胞分泌的IL-8的表达。
我们的研究首次证明直肠给予白云母可改善TNBS诱导的结肠炎的结肠炎症。需要进一步的验证性研究来证明白云母可能是治疗溃疡性结肠炎的潜在治疗药物。
