生长抑素对溃疡性结肠炎模型大鼠肠道炎性损伤的治疗作用

Therapeutic effects of somatostatin on the intestinal inflammatory injury in rat model of ulcerative colitis

目的:观察生长抑素(奥曲肽)对溃疡性结肠炎(ulcerative colitis,UC)大鼠模型的作用,初步探讨其可能机制.方法:♂SD大鼠随机分为正常对照组、奥曲肽对照组、模型组、治疗组,每组7只.模型组、治疗组大鼠用三硝基苯磺酸(TNBS)/乙醇溶液灌肠复制UC模型.观察各组实验大鼠体质量变化、大体及组织病理学改变.采用酶联免疫吸附法检测细胞因子(IL-6、IL-10、TNF-α)的含量、蛋白质印迹杂交法检测结肠组织NF-κBp65蛋白的表达.结果:生长抑素可以缓解大鼠体质量的减轻,减少腹泻及便血的发生,并且能够显著改善结肠组织大体和组织学评分.与正常组比较,模型组大鼠结肠黏膜IL-6、TNF-α表达明显升高(188.27±11.65ng/Lvs102.13±7.12ng/L,87.39±6.74ng/Lvs121.51±8.56ng/L,均P<0.01);IL-10表达明显下降(71.40±8.28ng/Lvs202.97±12.26ng/L,P<0.01);与模型组比较,治疗组大鼠结肠黏膜IL-6、TNF-α表达均明显降低(142.03±12.68ng/L,90.87±9.26ng/L,均P<0.01),IL-10表达明显升高(124.07±10.05ng/L,P<0.01).模型组结肠组织中NF-κB的蛋白含量明显高于治疗组(1059.60±96.35vs471.23±11.61,P<0.01).结论:生长抑素对TNBS诱导的大鼠溃疡性结肠炎具有显著治疗作用,其作用机制可能是通过影响炎症反应的信号通路NF-κB的活化,进而下调促炎细胞因子及上调抗炎细胞因子的产生和表达.

AIM： To study the therapeutic effects of somatostatin （octreotide） on 2, 4, 6-trinitrobenzene sulfonic acid induced ulcerative colitis （UC） in rats and to explore its possible mechanism. METHODS： Twenty-eight female SD rats were randomized into normal control group, octreotide control group, model group and treatment groups （7 rats for each group）. UC in model group and treatment group was induced by intrarectal administration of TNBS （100 mg/kg in 50% ethanol）. Octreotide 50 μg/kg per day （octreotide control group and treatment group） or saline 1 mL per day （normal control group and model group） was administered intraperitoneally each day for 14 days. All animals were killed on day 15. The body weight loss of each rat, macroscopical and histological changes of the colon were observed. IL-6, IL-10, tumor necrosis factor （TNF-α） in colon supernate were tested by ELISA and the expression of nuclear factor （NF）-κB p65 in the colonic tissues was detected using Western blot. RESULTS： Compared with the model group, somatostatin inhibited the body weight loss and occurrence of diarrhea as well as rectal bleeding in the rats, and significantly improved the macroscopic damage score and histological score in the treatment group. Compared with the normal group, colonic mucosal IL-6, TNF-α expression of model group rats were significantly increased （188.27 ± 11.65 ng/L vs 102.13 ± 7.12 ng/L, 121.51 ± 8.56 ng/L vs 87.39 ± 6.74 ng/L, both P 〈 0.01）; IL-10 expression was significantly decreased （71.40 ± 8.28 ng/L vs 202.97 ± 12.26 ng/L, P 〈 0.01）; Compared with the model group, mucosal IL-6, TNF-α expression of the treatment group rats colon were significantly lower （142.03 ± 12.68 ng/L, 90.87 ± 9.26 ng/L, both P 〈 0.01）, IL-10 expression was significantly elevated （124.07 ± 10.05 ng/L, P 〈 0.01）. For the model group, the colon tissue of NF-κB protein content was significantly higher than the treatment group （1059.60 ± 96.35 vs 471.23 ± 11.61, P 〈 0.01）. CONCLUSION： Somatostatin has noticeable therapeutic effects on TNBS-induced ulcerative colitis in rats. Suppressing NF-κB activation, decreas/ng the expression of proinflammatory cytokines and increasing the expression of anti-inflammatory cytokines may be the possible mechanism.