中药预处理对结肠炎模型大鼠的免疫调节效应

Immunomodulatory Effects on Colitis Model Rats Pretreated with Traditional Chinese Medicine

背景:免疫调节异常在炎症性肠病(IBD)的发病中起重要作用,中药免疫调节是IBD重要的潜在治疗策略之一。目的:探讨中药溃克灵在IBD发病中的免疫调节预防作用。方法:45只Sprague-Dawley大鼠随机分为3组,分别予溃克灵、硫唑嘌呤(AZA)和0.9%NaCl溶液灌胃1周。以三硝基苯磺酸(TNBS)诱导结肠炎模型,于造模第1和第4周分别处死大鼠,检测T细胞亚群,分别以放射免疫测定和酶联免疫吸附测定(ELISA)检测血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-10的变化,并行组织学评分。结果:造模后大鼠均出现腹泻症状。造模后第2周,溃克灵组大鼠体质量显著高于AZA组和正常对照组(P<0.05)。在炎症急性期,溃克灵组大鼠外周血CD4+/CD8+比值显著低于正常对照组(P<0.05),血清IL-1β水平、结肠组织学评分显著低于AZA组和正常对照组(P<0.05),血清IL-10水平显著高于正常对照组(P<0.05)。结论:短期应用中药溃克灵对模型大鼠结肠炎的发生具有一定预防保护作用,可能与下调CD4+/CD8+比值、抑制促炎因子IL-1β分泌和促进抗炎因子IL-10分泌等免疫调节机制有关。

Background： Immune dysregulation plays an important role in the pathogenesis of inflammatory bowel disease （IBD）. The immunomodulatory therapy with traditional Chinese medicine might become a potential strategy for IBD. Aims： To investigate the preventive immunomodulatory effects of traditional Chinese medicine Kuikeling on IBD. Methods： A total of 45 Sprague-Dawley rats were randomly divided into three groups, which were treated with Kuikeling, azathioprine （AZA） and 0.9% NaCl through stomach infusion for one week, respectively. Colitis model was then induced by trinitrobenzene sulfonic acid （TNBS）. The rats were killed separately on the 1st and 4th week, T lymphocyte subsets were determined, serum tumor necrosis factor （TNF）-α and interleukin （IL）-1β were measured by radioimmunoassay, and serum IL-10 was measured by enzyme-linked immunosorbent assay （ELISA）. The histological score of colon was also evaluated. Results： Rats that developed acute colitis showed the symptom of diarrhea. The body weight in Kuikeling group was significantly higher than that in AZA and normal control groups at the 2nd week after model construction （P〈0.05）. In the acute stage, peripheral blood CD4^＋/CD8^＋ ratio in Kuikeling group was markedly lower than that in normal control group （P〈0.05）, serum IL-1β and the histological score of colon were significantly lower than those in AZA and normal control groups （P〈0.05）. Serum level of IL-10 in Kuikeling group was significantly higher than that in normal control group （P〈0.05）. Conclusions： Short-term traditional Chinese medicine Kuikeling has potential protective effects on experimental colitis in rats. The mechanism may be due to down-regulation of CD4^＋/CD8^＋ ratio, suppression of secretion of proinflammatory cytokine IL-1β, and up-regulation of secretion of anti-inflammatory cytokine IL-10.