發(fā)布時(shí)間：2018-07-26 16:59

【摘要】：目的:通過(guò)建立葡聚糖硫酸鈉(dextran sulfate sodium,DSS)誘導(dǎo)的鼠結(jié)腸炎模型,探討alpha7煙堿型乙酰膽堿受體(alpha7 nicotinic acetylcholine receptor,α7n ACh R)激動(dòng)劑GTS-21改善模型鼠結(jié)腸炎癥的效果及可能機(jī)制。方法:8~10周齡SPF級(jí)雄性BALB/c小鼠隨機(jī)分為正常對(duì)照(CON)組、DSS模型組、GTS-21治療組(每組8只)。DSS模型組采用自由飲用含3.5%DSS水造模,治療組自由飲用3.5%DSS水,同時(shí)給予GTS-21[10 mg/(kg·d),腹腔注射],共7 d,對(duì)照組予生理鹽水,每天予各組鼠疾病活動(dòng)性評(píng)分(DAI評(píng)分)。第8天處死小鼠,觀察結(jié)腸黏膜組織大體改變并測(cè)其長(zhǎng)度、濕重,HE染色后行腸組織學(xué)炎癥(HI)評(píng)分;細(xì)胞因子芯片篩選變化的細(xì)胞因子;ELISA法進(jìn)一步檢測(cè)芯片篩選出的變化明顯的細(xì)胞因子。結(jié)果:(1)DSS組鼠結(jié)腸長(zhǎng)度變短[(8.22±0.37)cm vs.(11.65±0.30)cm,n=8,P0.001],DAI評(píng)分較正常組增高[(1.51±0.10)分vs.0分,n=8,P0.001],HI評(píng)分升高[(20.5±3.9)分vs.(0.9±0.4)分,n=8,P0.001],表明造模成功;(2)給予煙堿型乙酰膽堿受體激動(dòng)劑GTS-21的DSS模型鼠,DAI評(píng)分下降[(0.25±0.10)分vs.(1.51±0.10)分,n=8,P0.001];結(jié)腸長(zhǎng)度較DSS組改善[(9.42±0.32)cm vs.(8.22±0.37)cm,n=8,P0.05];HI評(píng)分減低[(7.5±2.0)分vs(20.5±3.9)分,n=8,P0.01],提示GTS-21能改善DSS誘導(dǎo)的鼠結(jié)腸炎癥;(3)細(xì)胞因子芯片篩選實(shí)驗(yàn)結(jié)果表明,DSS組γ干擾素誘導(dǎo)單核細(xì)胞因子(monokine induced by IFN-γ,CXCL9/Mig)升高最明顯,此外腫瘤壞死因子α(tumor necrosis factor alpha,TNF-α)、白細(xì)胞介素1β(interleukin 1β,IL-1β)、γ-干擾素(interferonγ,IFN-γ)也明顯升高;(4)進(jìn)一步ELISA檢測(cè)芯片變化最明顯的CXCL9/Mig,發(fā)現(xiàn)DSS組鼠血清CXCL9/Mig明顯升高(P0.05),給予GTS-21后,血清CXCL9/Mig降低(P0.05)。結(jié)論:GTS-21能減輕實(shí)驗(yàn)結(jié)腸炎鼠腸道炎癥,該作用可能與減低趨化因子CXCL9/Mig水平,進(jìn)而減少炎癥細(xì)胞的腸道聚集有關(guān)。
[Abstract]:Aim: to investigate the effect and mechanism of alpha7 nicotinic acetylcholine receptor (alpha7 nicotinic acetylcholine receptor, 偽 7n ACh R) agonist GTS-21) on the improvement of rat colitis induced by dextran sodium sulfate (dextran sulfate sodium). Methods male BALB/c mice of SPF grade 10 weeks old were randomly divided into two groups: normal control group (CON) group, n = 8). DSS model group (n = 8 in each group). The model group was made by free drinking of 3.5%DSS water, and the treatment group was free to drink 3.5%DSS water. At the same time, GTS-21 [10 mg/ (kg d), intraperitoneal injection] was given to the control group for 7 days. The control group was given normal saline, and the disease activity score (DAI score) was given to the rats in each group every day. On the 8th day, the mice were killed, the colonic mucosa was observed and the length of colonic mucosa was measured. The (HI) score of intestinal histologic inflammation was obtained after HE staining. Cytokines were screened by cytokine microarray and the cytokines were further detected by Elisa. Results: (1) the colonic length of DSS group was shorter [(8.22 鹵0.37) cm vs. (11.65 鹵0.30) cm ~ (-1) + 0.30) cm vs. (] Dai score was higher than that of normal group [(1.51 鹵0.10) vs.0 score (n = 8) P _ (0.001)] hi score increased [(20.5 鹵3.9) vs (0.9 鹵0.4) vs. (0.9 鹵0.4) min ~ (8) P _ (0.001)], and (2) the DSS model rats treated with nicotinic acetylcholine receptor agonist GTS-21 (0.25 鹵0.10) scores decreased [(0.25 鹵0.10) scores vs. (1. 51 鹵0. 10) vs (1. 51 鹵0. 10)] Compared with the DSS group, the colon length was improved [(9.42 鹵0.32) cm vs. (8.22 鹵0.37) cm P0.01] and the HI score was decreased [(7.5 鹵2.0) points vs (20.5 鹵3.9) min P0.01], indicating that GTS-21 could improve the DSS induced colitis in rats. (3) the results of cytokine microarray screening showed that the monocyte factor (monokine induced by IFN- 緯 CXCL9Mig increased most significantly in the DSS group. In addition, tumor necrosis factor 偽 (tumor necrosis factor alpha-TNF- 偽, interleukin-1 尾 (interleukin 1 尾 -IL-1 尾) and interferon 緯 (interferon 緯 -IFN- 緯) were also significantly increased. (4) the most obvious changes of CXCL9 / Mig were further detected by ELISA. It was found that the serum CXCL9/Mig in DSS group was significantly increased (P0.05), and the serum CXCL9/Mig was decreased after GTS-21 administration (P0.05). ConclusionTwo one GTS-21 can attenuate the intestinal inflammation in experimental colitis rats, which may be related to the reduction of chemokine CXCL9/Mig level and the reduction of intestinal aggregation of inflammatory cells.
【作者單位】： 南京醫(yī)科大學(xué)第一附屬醫(yī)院消化科;
【基金】：國(guó)家自然科學(xué)基金(81270469)
【分類號(hào)】：R574.62
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本文編號(hào)：2146676