CCR5第一、二胞外环特异性结合的拮抗短肽对TNBS诱导SD大鼠结肠炎的治疗作用

发布时间：2018-06-27 23:18

本文选题：C-C趋化因子受体 + 拮抗肽　；参考：《中国病理生理杂志》2017年05期

【摘要】：目的:研究C-C趋化因子受体5(CCR5)膜外第一、二胞外环(ECL1和ECL2)特异性结合的拮抗短肽对三硝基苯磺酸(TNBS)诱导的结肠炎模型大鼠的治疗作用与机制。方法:采用100 mg/kg TNBS诱导结肠炎SD大鼠模型;用不同剂量的2条拮抗短肽(ECL1:25、35和45 mg/kg;ECL2:15、25和35 mg/kg)分别作用于模型大鼠,观察其对大鼠疾病活动指数(DAI)、结肠大体损伤指数(CMDI)和组织病理学改变的影响,采用real-time PCR和Western blot法分别检测结肠组织TNF-α和COX-2的mRNA与蛋白表达水平。结果:与模型组相比,有效剂量的ECL2拮抗短肽HY治疗组大鼠疾病活动程度、肠道溃疡及病理组织学损伤均有明显减轻,各评分指数差异具有统计学意义(P0.05);TNF-α和COX-2的蛋白和mRNA表达水平均明显下降(P0.05)。ECL1拮抗短肽GH作用的大鼠结肠炎症状评分及TNF-α和COX-2炎症因子表达无明显改变。结论:ECL2拮抗短肽可能通过下调结肠黏膜TNF-α和COX-2的表达来缓解TNBS诱导的SD大鼠结肠炎,而ECL1拮抗短肽的作用不明显。
[Abstract]:Aim: to study the therapeutic effect and mechanism of C-C chemokine receptor 5 (CCR5) extracellular first and second extracellular rings (ECL1 and ECL2) on TNBS induced colitis in rats. Methods: SD rat model of colitis was induced by 100 mg/kg TNBS and treated with two antagonistic short peptides (ECL 1: 25 and 45 mg / kg ECL 2: 1525 and 35 mg/kg respectively). The changes of disease activity index (Dai), colon gross injury index (CMDI) and histopathological changes were observed. The expression of TNF- 伪 and COX-2 mRNA and protein were detected by real-time PCR and Western blot. Results: compared with the model group, the active degree of disease, intestinal ulcer and histopathological injury were significantly alleviated in the group treated with ECL2 antagonistic peptide HY. The expression levels of protein and mRNA of TNF- 伪 and COX-2 were significantly decreased (P0.05). ECL1 antagonized short peptide GH on the symptom score of colitis and the expression of TNF- 伪 and COX-2 inflammatory factors in rats. Conclusion the antagonistic short peptide of ECL2 may alleviate TNBS induced colitis in SD rats by down-regulating the expression of TNF- 伪 and COX-2 in colon mucosa, but ECL1 has no obvious antagonistic effect on short peptide.
【作者单位】：中山大学孙逸仙纪念医院消化内科;中山大学孙逸仙纪念医院病理科;中山大学孙逸仙纪念医院儿科;
【基金】：国家自然科学基金资助项目(No.81370499) 广东省自然科学基金资助项目(No.2014A030313020;No.2016A03031343)
【分类号】：R574.62

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