文章摘要
朱云娟,马晶晶,赵小静,张迎娣,马海琴,张红杰.烟碱型乙酰胆碱受体激动剂GTS-21对鼠实验性结肠炎的影响[J].南京医科大学学报,2017,(4):428~433
烟碱型乙酰胆碱受体激动剂GTS-21对鼠实验性结肠炎的影响
Effects of nicotinic acetylcholine receptor agonist GTS-21 on DSS-induced colitis
投稿时间:2016-10-31  
DOI:10.7655/NYDXBNS20170409
中文关键词: DSS诱导结肠炎  alpha7烟碱型乙酰胆碱受体  GTS-21  CXCL9/Mig
英文关键词: DSS-induced colitis  α7 nicotinic acetylcholine receptors  GTS-21  CXCL9/Mig
基金项目:国家自然科学基金(81270469)
作者单位
朱云娟 南京医科大学第一附属医院消化科江苏 南京 210029 
马晶晶 南京医科大学第一附属医院消化科江苏 南京 210029 
赵小静 南京医科大学第一附属医院消化科江苏 南京 210029 
张迎娣 南京医科大学第一附属医院消化科江苏 南京 210029 
马海琴 南京医科大学第一附属医院消化科江苏 南京 210029 
张红杰 南京医科大学第一附属医院消化科江苏 南京 210029 
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中文摘要:
      目的:通过建立葡聚糖硫酸钠(dextran sulfate sodium,DSS)诱导的鼠结肠炎模型,探讨alpha7烟碱型乙酰胆碱受体(alpha7 nicotinic acetylcholine receptor,α7nAChR)激动剂GTS-21改善模型鼠结肠炎症的效果及可能机制。方法:8~10 周龄 SPF级雄性BALB/c小鼠随机分为正常对照(CON)组、DSS模型组、GTS-21治疗组(每组8只)。DSS模型组采用自由饮用含3.5%DSS水造模,治疗组自由饮用3.5%DSS水,同时给予GTS-21[10 mg/(kg·d),腹腔注射],共7 d,对照组予生理盐水,每天予各组鼠疾病活动性评分(DAI评分)。第8天处死小鼠,观察结肠黏膜组织大体改变并测其长度、湿重,HE染色后行肠组织学炎症(HI)评分;细胞因子芯片筛选变化的细胞因子;ELISA法进一步检测芯片筛选出的变化明显的细胞因子。结果:①DSS组鼠结肠长度变短[(8.22± 0.37)cm vs.(11.65±0.30)cm,n=8,P<0.001],DAI评分较正常组增高[(1.51±0.10)分 vs.0分,n=8,P<0.001],HI评分升高[(20.5± 3.9)分 vs.(0.9± 0.4)分,n=8,P<0.001],表明造模成功;②给予烟碱型乙酰胆碱受体激动剂GTS-21的DSS模型鼠,DAI评分下降[(0.25±0.10)分 vs.(1.51±0.10)分,n=8,P<0.001];结肠长度较DSS组改善[(9.42± 0.32)cm vs.(8.22± 0.37)cm,n=8,P<0.05];HI评分减低[(7.5± 2.0)分 vs(20.5± 3.9)分,n=8,P<0.01],提示GTS-21能改善DSS诱导的鼠结肠炎症;③细胞因子芯片筛选实验结果表明,DSS组γ干扰素诱导单核细胞因子(monokine induced by IFN-γ,CXCL9/Mig)升高最明显,此外肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α)、白细胞介素1β(interleukin 1β,IL-1β)、γ-干扰素(interferon γ,IFN-γ)也明显升高;④进一步ELISA检测芯片变化最明显的CXCL9/Mig,发现DSS组鼠血清CXCL9/Mig明显升高(P<0.05),给予GTS-21后,血清CXCL9/Mig降低(P<0.05)。结论:GTS-21能减轻实验结肠炎鼠肠道炎症,该作用可能与减低趋化因子CXCL9/Mig水平,进而减少炎症细胞的肠道聚集有关。
英文摘要:
      Objective:To investigate whether the α7 nicotinic acetylcholine receptors agonist GTS-21 can ameliorate dextran sulfate sodium(DSS)-induced colitis and its potential mechanism. Methods:Male BALB/c mice(8-10 weeks old) were randomly divided into 3 groups,including the control group,the DSS-induced group,and the GTS-21 treatment group(n=8,each group). DSS model was performed with 3.5% DSS free drink,the GTS-21 treatment group was performed with 3.5% DSS free drink+GTS-21 10 mg/(kg·d),ip,for 7 d. The control group was given normal saline,and DAI score was given to each group for every day. At day 8,all mice were sacrificed,the changes of the colonic mucosa were observed,the length and wet weight were measured,and the histological inflammation(HI) score was assessed by HE staining. The levels of cytokines were detected by ELISA. Results:①Compared with the control mice,DAI score was increased[(1.51±0.10)vs.0,n=8,P<0.001],colon length was shortened[(8.22±0.37)cm vs.(11.65±0.30)cm,n=8,P<0.001] and HI score was increased[(20.5±3.9)vs.(0.9±0.4),n=8,P<0.001]in mice-induced DSS,which showed that the model was successfully established.②Compared with DSS-induced mice,DAI score was decreased[(0.25±0.10)vs.(1.51±0.10),n=8,P<0.001],shortened colon length was improved[(9.42±0.32)cm vs.(8.22±0.37)cm,n=8,P<0.05] and HI score was decreased[(7.5±2.0)vs.(20.5± 3.9),n=8,P<0.01] in mice with administration of GTS-21,which suggested that GTS-21 improved DSS-induced colitis in mice.③The level of CXCL9/Mig in DSS-induced mice was increased,while it was significantly decreased in mice with administration of GTS-21. In addition,tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β) and interferon γ(IFN-γ) were significantly increased. ④CXCL9/Mig with the most obvious change detected by further ELISA showed that serum CXCL9/Mig increased significantly in the DSS group(P<0.05),and after administration of GTS-21,serum CXCL9/Mig was decreased(P<0.05). Conclusion:α7nAChR agonist GTS-21 can attenuate the intestinal inflammation in DSS-induced mice,which may be due to reduction of CXCL9/Mig(a chemotactic factor),and then reduction of inflammatory cell aggregation.
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