乐复能对溃疡性结肠炎小鼠疗效及其对小鼠结肠黏膜内TNF-α表达的影响

发布时间：2018-11-12 20:42

【摘要】：目的:观察乐复能对葡聚糖硫酸钠(dextran sulfate sodium,DSS)诱导的实验性溃疡性结肠炎(ulcerative colitis,UC)小鼠模型的治疗作用及其对小鼠结肠黏膜中肿瘤坏死因子-α(tumour necrosis factor alpha,TNF-α)表达的影响,了解乐复能对UC的治疗作用及可能的机制。方法:70只Balb/C雌性小鼠,8周龄左右,体质量18~22 g/只,清洁级。随机分为7组,分别为正常组、模型组、美沙拉嗪治疗组、泼尼松治疗组以及乐复能低、中、高剂量组,每组10只。采用4%DSS水溶液自由饮用的造模方法制作UC小鼠模型。造模第8天,各组同时分别给予对照剂与实验药物,实验第14天处死小鼠,游离并取出全段结肠,测量回盲部至肛门的长度,记录小鼠疾病活动指数(disease activity index,DAI)、结肠长度、组织学损伤评分、结肠黏膜组织中TNF-α的表达。结果:1)使用DSS的各干预组小鼠均不同程度地出现腹泻、黏液便、大便隐血阳性或血便等症状,随天数增加,小鼠DAI积分逐渐增高。美沙拉嗪、泼尼松、乐复能均能改善小鼠的一般状况,降低小鼠的DAI评分,减轻结肠长度缩短情况,降低组织学损伤评分。2)乐复能低、中、高剂量组,美沙拉嗪组及泼尼松组DAI积分与模型组相比,差异均有统计学意义(均P0.01);美沙拉嗪组、泼尼松组与乐复能低剂量组之间比较,差异均无统计学意义(均P0.05),乐复能中、高剂量组治疗效果明显好于美沙拉嗪组、泼尼松组与乐复能低剂量组(均P0.01),且乐复能治疗效果呈剂量依赖性,乐复能高剂量组好于乐复能中剂量组(P0.01)。3)乐复能低、中、高剂量组、泼尼松组、美沙拉嗪组黏膜缺损相对较轻,小部分腺体不完整,炎症细胞较少,与模型组比较,差异有统计学意义(均P0.01);乐复能高剂量组与乐复能低、中剂量组,美沙拉嗪组与泼尼松组比较,组织损伤明显减轻,组织学评分显著降低,差异均有统计学意义(均P0.05);但在乐复能低、中剂量组,美沙拉嗪组和泼尼松组之间差异均无统计学意义(均P0.05)。4)乐复能低、中、高剂量组,美沙拉嗪及泼尼松处理组TNF-α的表达明显下调,与模型组相比较,差异均有统计学意义(均P0.01);美沙拉嗪组与泼尼松组比较,TNF-α表达差异无统计学意义(P0.05),乐复能低、中、高剂量组之间TNF-α的表达随着剂量增加而减少,所有乐复能治疗组TNF-α的表达均明显低于其它治疗组(均P0.01)。结论:乐复能能明显改善DSS诱导的UC小鼠DAI评分、小鼠结肠黏膜损伤情况及炎症评分,下调小鼠结肠黏膜组组织内TNF-α的表达,其结果优于美沙拉嗪与泼尼松,且乐复能的作用呈剂量依赖性。
[Abstract]:Objective: to observe the therapeutic effect of Lefoneng on experimental ulcerative colitis (ulcerative colitis,UC) mice induced by sodium dextran sulfate (dextran sulfate sodium,DSS) and its effect on tumor necrosis factor- 伪 (tumour necrosis factor alpha, in colonic mucosa of mice. To understand the therapeutic effect of Lefoneng on UC and its possible mechanism. Methods: 70 Balb/C female mice, about 8 weeks old, with body weight of 1822 g / mouse, clean grade. They were randomly divided into 7 groups: normal group, model group, mesalazine group, prednisone group and low, medium and high dose groups with 10 rats in each group. The model of UC mice was made by the method of free drinking of 4%DSS aqueous solution. On the 8th day, the mice were killed on the 14th day. The length of ileocecum to anus was measured, and the disease activity index (disease activity index,DAI) was recorded. Colonic length, histological injury score and expression of TNF- 伪 in colonic mucosa. Results: 1) diarrhea, mucus stool, fecal occult blood positive or blood stool were found in all the intervention groups treated with DSS. With the increase of days, the DAI score of mice increased gradually. Mesalazine, prednisone and lofenac can all improve the general condition of mice, reduce the DAI score, reduce the shortening of colon length, and decrease the histological injury score. 2) the low, middle and high doses of Lefenone can improve the general condition of mice, reduce the colonic length of mice, and decrease the score of histological injury. Compared with the model group, the DAI scores in the mesalazine group and prednisone group were significantly different (P0.01). There was no significant difference between prednisone group and low dose group (P0.05). The therapeutic effect of high dose group was significantly better than that of mesalazine group. Prednisone group and lofenac low dose group (all P0.01), and the effect of lofenac in a dose-dependent manner, the high dose group was better than the middle dose group (P0.01). 3) the low, medium, high dose, prednisone group, the high dose group, the prednisone group, and the low dose group, the high dose group, the prednisone group. Compared with the model group, the mucosal defect of mesalazine group was relatively light, the small portion of glands was incomplete, and the inflammatory cells were less (P0.01). Compared with prednisone group, the tissue injury in high dose group and low group in middle dose group, mesalazine group and prednisone group were significantly alleviated, and the histological score was significantly decreased (P0.05). However, there was no significant difference between middle dose group, mesalazine group and prednisone group (P0.05). The expression of TNF- 伪 in medium, high dose, mesalazine and prednisone groups was significantly down-regulated. Compared with the model group, the difference was statistically significant (P0.01). Compared with prednisone group, there was no significant difference in the expression of TNF- 伪 between mesalazine group and prednisone group (P0.05). The expression of TNF- 伪 in medium and high dose groups decreased with the increase of dose. The expression of TNF- 伪 in all the lofenac groups was significantly lower than that in other treatment groups (all P 0.01). Conclusion: lofenac can significantly improve the DAI score, colonic mucosal injury and inflammation score of UC mice induced by DSS, and down-regulate the expression of TNF- 伪 in colonic mucosa of mice. The results are superior to those of mesalazine and prednisone. The effect of Lefeng was dose-dependent.
【作者单位】：中南大学湘雅医院消化内科;
【分类号】：R574.62

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