本文選題：潰瘍性結(jié)腸炎　切入點(diǎn)：DPP-4抑制劑　出處：《山東大學(xué)》2014年碩士論文

【摘要】：目的 1.探討DPP-4抑制劑對(duì)小鼠潰瘍性結(jié)腸炎(UC)的療效；2、探討DPP-4抑制劑與SASP聯(lián)合用藥治療小鼠UC是否存在協(xié)同作用；3.通過ELISA法檢測(cè)小鼠血清TNF-α、IL-10、胰高血糖素樣肽-2(GLP-2)水平,初步探討DPP-4抑制劑治療小鼠UC的機(jī)制。 方法 將30只雄性BALB/c小鼠按照隨機(jī)分組原則平均分為5組：空白對(duì)照組、模型對(duì)照組、SASP治療組、DPP-4抑制劑治療組、DPP-4抑制劑和SASP聯(lián)合治療組(簡稱聯(lián)合治療組)。除空白對(duì)照組外,其他各組用5%葡聚糖硫酸鈉(DSS)誘導(dǎo)小鼠UC模型,空白對(duì)照組和模型對(duì)照組給予0.5%羧甲基纖維素(CMC)灌胃,DPP-4抑制劑治療組、SASP治療組、聯(lián)合治療組分別給予西格列汀、SASP、西格列汀和SASP兩者聯(lián)合灌胃治療,1次/d,連續(xù)6d。每天觀察小鼠的臨床癥狀,稱量小鼠體質(zhì)量,觀察大便性狀,鄰聯(lián)甲苯胺法檢測(cè)大便隱血情況,計(jì)算疾病活動(dòng)指數(shù)(DAI)值。實(shí)驗(yàn)進(jìn)行6d后處死小鼠,剖腹分離結(jié)腸組織,測(cè)量結(jié)腸長度,結(jié)腸HE染色進(jìn)行病理組織學(xué)觀察,檢測(cè)結(jié)腸髓過氧化物酶(MPO)活性,摘眼球取血,采用ELISA法檢測(cè)小鼠血清TNF-α、IL-10、GLP-2水平。 結(jié)果 與空白對(duì)照組相比,模型對(duì)照組小鼠逐漸出現(xiàn)體質(zhì)量下降、稀便、血便、少動(dòng)、精神萎靡、毛發(fā)散亂等臨床癥狀,DAI指標(biāo)顯著升高(P0.01),結(jié)腸長度顯著縮短(P0.01),結(jié)腸病理損傷明顯加重,結(jié)腸MPO活性顯著升高(P0.01),血清TNF-α、IL-10、GLP-2水平均顯著升高(P0.01)。與模型對(duì)照組相比,DPP-4抑制劑治療組、SASP治療組、聯(lián)合治療組均明顯改善UC小鼠臨床癥狀,DAI評(píng)分顯著降低(P0.05),結(jié)腸長度明顯增加(P0.05),結(jié)腸病理損傷明顯緩解,結(jié)腸MPO活性顯著降低(P0.01),血清TNF-α水平顯著降低(P0.01)；DPP-4抑制劑治療組和聯(lián)合治療組血清GLP-2水平顯著升高(P0.01); SASP治療組及聯(lián)合治療組血清IL-10水平顯著升高(P0.01)。與DPP-4抑制劑治療組相比,聯(lián)合治療組小鼠DAI評(píng)分顯著降低(P0.05),結(jié)腸長度明顯增加(P0.05),結(jié)腸MPO活性顯著降低(P0.05),血清TNF-α水平顯著降低(P0.01),血清IL-10水平顯著升高(P0.01)。與SASP治療組相比,聯(lián)合治療組DAI指標(biāo)有降低趨勢(shì)、結(jié)腸長度有增加趨勢(shì),但差異均無統(tǒng)計(jì)學(xué)意義(P0.05),結(jié)腸MPO活性、血清TNF-α水平顯著降低(P0.05),血清GLP-2水平顯著升高(P0.01). DPP-4抑制劑治療組與SASP治療組相比,DAI指標(biāo)、結(jié)腸長度、結(jié)腸MPO活性均無顯著差異(P0.05), SASP治療組血清TNF-α水平顯著降低(P0.05)、血清IL-10水平顯著升高(P0.01)、血清GLP-2顯著降低(P0.01)。 結(jié)論 DPP-4抑制劑通過抗炎和升高血清GLP-2水平,達(dá)到修復(fù)結(jié)腸炎黏膜損傷的作用,對(duì)小鼠UC有明顯的治療作用,其抗炎機(jī)制不依賴于IL-10,與SASP作用機(jī)制不同,DPP-4抑制劑與SASP聯(lián)合用藥,在治療小鼠UC方面存在協(xié)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- 偽 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- 偽 -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- 偽 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- 偽 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- 偽 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- 偽 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.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R574.62

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