DPP-4抑制剂联合SASP治疗小鼠溃疡性结肠炎的疗效

发布时间：2018-04-09 10:00

本文选题：溃疡性结肠炎　切入点：DPP-4抑制剂　出处：《山东大学》2014年硕士论文

【摘要】：目的 1.探讨DPP-4抑制剂对小鼠溃疡性结肠炎(UC)的疗效；2、探讨DPP-4抑制剂与SASP联合用药治疗小鼠UC是否存在协同作用；3.通过ELISA法检测小鼠血清TNF-α、IL-10、胰高血糖素样肽-2(GLP-2)水平,初步探讨DPP-4抑制剂治疗小鼠UC的机制。方法将30只雄性BALB/c小鼠按照随机分组原则平均分为5组：空白对照组、模型对照组、SASP治疗组、DPP-4抑制剂治疗组、DPP-4抑制剂和SASP联合治疗组(简称联合治疗组)。除空白对照组外,其他各组用5%葡聚糖硫酸钠(DSS)诱导小鼠UC模型,空白对照组和模型对照组给予0.5%羧甲基纤维素(CMC)灌胃,DPP-4抑制剂治疗组、SASP治疗组、联合治疗组分别给予西格列汀、SASP、西格列汀和SASP两者联合灌胃治疗,1次/d,连续6d。每天观察小鼠的临床症状,称量小鼠体质量,观察大便性状,邻联甲苯胺法检测大便隐血情况,计算疾病活动指数(DAI)值。实验进行6d后处死小鼠,剖腹分离结肠组织,测量结肠长度,结肠HE染色进行病理组织学观察,检测结肠髓过氧化物酶(MPO)活性,摘眼球取血,采用ELISA法检测小鼠血清TNF-α、IL-10、GLP-2水平。结果与空白对照组相比,模型对照组小鼠逐渐出现体质量下降、稀便、血便、少动、精神萎靡、毛发散乱等临床症状,DAI指标显著升高(P0.01),结肠长度显著缩短(P0.01),结肠病理损伤明显加重,结肠MPO活性显著升高(P0.01),血清TNF-α、IL-10、GLP-2水平均显著升高(P0.01)。与模型对照组相比,DPP-4抑制剂治疗组、SASP治疗组、联合治疗组均明显改善UC小鼠临床症状,DAI评分显著降低(P0.05),结肠长度明显增加(P0.05),结肠病理损伤明显缓解,结肠MPO活性显著降低(P0.01),血清TNF-α水平显著降低(P0.01)；DPP-4抑制剂治疗组和联合治疗组血清GLP-2水平显著升高(P0.01); SASP治疗组及联合治疗组血清IL-10水平显著升高(P0.01)。与DPP-4抑制剂治疗组相比,联合治疗组小鼠DAI评分显著降低(P0.05),结肠长度明显增加(P0.05),结肠MPO活性显著降低(P0.05),血清TNF-α水平显著降低(P0.01),血清IL-10水平显著升高(P0.01)。与SASP治疗组相比,联合治疗组DAI指标有降低趋势、结肠长度有增加趋势,但差异均无统计学意义(P0.05),结肠MPO活性、血清TNF-α水平显著降低(P0.05),血清GLP-2水平显著升高(P0.01). DPP-4抑制剂治疗组与SASP治疗组相比,DAI指标、结肠长度、结肠MPO活性均无显著差异(P0.05), SASP治疗组血清TNF-α水平显著降低(P0.05)、血清IL-10水平显著升高(P0.01)、血清GLP-2显著降低(P0.01)。结论 DPP-4抑制剂通过抗炎和升高血清GLP-2水平,达到修复结肠炎黏膜损伤的作用,对小鼠UC有明显的治疗作用,其抗炎机制不依赖于IL-10,与SASP作用机制不同,DPP-4抑制剂与SASP联合用药,在治疗小鼠UC方面存在协同作用。
[Abstract]:Purpose1.To investigate the therapeutic effect of DPP-4 inhibitor on ulcerative colitis in mice and to explore whether there is a synergistic effect of DPP-4 inhibitor and SASP in the treatment of UC in mice.The levels of serum TNF- 伪 IL-10 and glucagon like peptide-2 (GLP-2) in mice were detected by ELISA method, and the mechanism of DPP-4 inhibitor in the treatment of UC in mice was preliminarily investigated.MethodThirty male BALB/c mice were divided into five groups according to the principle of random grouping: blank control group, model control group, DPP-4 inhibitor treatment group and SASP combined treatment group.In addition to the blank control group, the other groups were treated with 5% dextran sodium sulfate (DSS) to induce mouse UC model. The blank control group and the model control group were given 0.5% carboxymethylcellulose (CMCc) intragastric perfusion with DPP-4 inhibitor to treat the mice with SASP.The combined treatment group was treated with siglitazone SASP, siglitatin and SASP for 6 consecutive days.The clinical symptoms of the mice were observed daily, the body mass of the mice was weighed, and the fecal traits were observed. The fecal occult blood was detected by o-bimethylaniline method, and the disease activity index (DAI) was calculated.ResultThe activity of MPO in colon and serum TNF- 伪 -IL-10 and GLP-2 levels were significantly increased (P 0.01).Compared with the model control group, the treatment group treated with DPP-4 inhibitor and SASP group, the combined treatment group significantly improved the clinical symptoms of UC mice. The Dai score decreased significantly, the colonic length increased significantly, and the colonic pathological injury was alleviated.The activity of MPO in colon decreased significantly, the level of TNF- 伪 in serum decreased significantly, the level of serum GLP-2 increased significantly in the treatment group and combined treatment group, and the level of serum IL-10 in the SASP treatment group and the combined treatment group increased significantly (P0.01).Compared with the DPP-4 inhibitor group, the DAI score, colon length, colon MPO activity, serum TNF- 伪 level and serum IL-10 level in the combined treatment group were significantly lower than those in the control group, respectively.Compared with the SASP treatment group, the DAI index and colon length in the combined treatment group were decreased and colon length was increased, but the difference was not statistically significant (P 0.05), the activity of MPO in colon, the level of serum TNF- 伪 decreased significantly (P 0.05), and the level of serum GLP-2 increased significantly (P 0.01).Compared with SASP treatment group, there was no significant difference in Dai index, colon length and colon MPO activity between DPP-4 inhibitor group and SASP group. Serum TNF- 伪 level in SASP group was significantly lower than that in SASP group. Serum IL-10 level was significantly higher than that in SASP treatment group, and serum GLP-2 level was significantly lower than that in SASP treatment group.ConclusionDPP-4 inhibitor can repair the mucosal injury of colitis by anti-inflammation and raising the level of serum GLP-2, and has obvious therapeutic effect on UC in mice. Its anti-inflammatory mechanism is not dependent on IL-10, which is different from the mechanism of SASP and the combination of DPP-4 inhibitor and SASP.There is a synergistic effect in the treatment of UC in mice.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R574.62

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