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重组旋毛虫半胱氨酸蛋白酶抑制剂对三硝基苯磺酸诱导的实验性肠炎的影响。

Effect of recombinant Trichinella spiralis cysteine proteinase inhibitor on TNBS-induced experimental inflammatory bowel disease in mice.

机构信息

Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Street, Harbin 150030, China.

Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Street, Harbin 150030, China.

出版信息

Int Immunopharmacol. 2019 Jan;66:28-40. doi: 10.1016/j.intimp.2018.10.043. Epub 2018 Nov 9.

Abstract

Inflammatory bowel disease (IBD) is a chronic autoimmune disease with a high recurrence rate. Ulcerative colitis (UC) and Crohn's disease (CD) are two types of IBD. At present, parasite-derived cysteine protease inhibitors have received extensive attention from researchers, and experiments have confirmed that these protease have an effect on certain autoimmune diseases. So we conducted experiments to investigate the effect of Trichinella spiralis cysteine protease inhibitors on TNBS-induced mouse CD models. In this experiment, 72 male BALB/c mice aged 6-8 weeks were randomly divided into two groups: prevention group and therapy group. The mice were sacrificed and harvested on the 7th day after the model was established to measure the changes of various indicators of colitis. The comparison of the TsCystatin + TNBS group with the PBS + TNBS group showed that the DAI score, MPO activity, and colonic macroscopic and microscopic damage significantly reduced, IFN-γ significantly decreased, IL-4 expression increased, and NF-κB expression decreased. The percentage of CD4+CD25+Foxp3+ Treg and CD8+CD28- Treg in spleen, and the proportion of CD4+/CD8+ Treg cells decreased. In the therapy group, we found no significant difference between the TNBS+PBS group and TNBS + TsCystatin group. Treatment with TsCystatin exerted a good intervention effect on the TNBS-induced mouse CD model. TsCystatin possibly induced a Th2-type immune response in the body, which balanced the Th1-type immune response induced by TNBS administration, thereby relieving colitis.

摘要

炎症性肠病(IBD)是一种慢性自身免疫性疾病,复发率高。溃疡性结肠炎(UC)和克罗恩病(CD)是两种 IBD。目前,寄生虫来源的半胱氨酸蛋白酶抑制剂受到了研究人员的广泛关注,实验证实这些蛋白酶对某些自身免疫性疾病有作用。因此,我们进行了实验来研究旋毛虫半胱氨酸蛋白酶抑制剂对 TNBS 诱导的小鼠 CD 模型的影响。在本实验中,将 72 只 6-8 周龄雄性 BALB/c 小鼠随机分为预防组和治疗组。在建立模型后第 7 天处死并采集小鼠,测量结肠炎各项指标的变化。与 PBS+TNBS 组相比,TsCystatin+TNBS 组的 DAI 评分、MPO 活性、结肠大体和显微镜下损伤明显减轻,IFN-γ 明显降低,IL-4 表达增加,NF-κB 表达降低。脾中 CD4+CD25+Foxp3+Treg 和 CD8+CD28-Treg 的比例以及 CD4+/CD8+Treg 细胞的比例下降。在治疗组中,我们发现 TNBS+PBS 组和 TNBS+TsCystatin 组之间没有显著差异。TsCystatin 对 TNBS 诱导的小鼠 CD 模型有较好的干预作用。TsCystatin 可能在体内诱导了 Th2 型免疫反应,平衡了 TNBS 给药诱导的 Th1 型免疫反应,从而缓解结肠炎。

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