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论文题名(中文):

 基于2013年~2016年新农合数据研究溃疡性结肠炎的流行趋势及棕榈酸对结肠炎症及上皮间质转化的影响初探    

姓名:

 刘婷婷    

论文语种:

 chi    

学位:

 博士    

学位类型:

 学术学位    

学位授予单位:

 北京协和医学院    

学校:

 北京协和医学院    

院系:

 请选择    

专业:

 临床医学    

指导教师姓名:

 杨红    

论文完成日期:

 2022-06-02    

关键词(中文):

 溃疡性结肠炎 发病率 患病率 环境危险因素 棕榈酸    

关键词(外文):

 ulcerative colitis incidence prevalence environmental risk factors palmitic acid    

论文文摘(中文):
研究目的:溃疡性结肠炎(ulcerative colitis, UC)是一种导致消化道炎症的慢性特发性疾病,疾病负担沉重,研究表明我国的 UC 发病率增长,但作为农业大国,我国农村地区的 UC 流行病学数据缺乏。因此本研究第一部分拟基于 2013 年~2016 年北京市、海南省新型农村合作医疗保险数据描述农村地区 UC 的发病率、患病率及变化趋势。而防控环境危险因素是应对我国 UC 发病率增长的主要任务,饮食西方化作为重要的环境危险因素,其中的高脂成分对 UC 的作用有待明确。因此第二部分以饱和脂肪酸棕榈酸(palmitic acid, PA)为研究对象初探其对结肠炎症及上皮间质转化(epithelial-to-mesenchymal transition, EMT)的影响。综上,本研究旨在进一步评估我国 UC 疾病负担,并为 UC 危险因素提供基础研究的证据,从而为卫生经济政策和防控策略提供理论依据。研究方法:1. 数据来源于 2013 年~2016 年北京市、海南省新农合数据库,按照所制定关键词筛选诊断 UC 的患者子集,提取新发病例、患病病例及费用数据,估算发病率(设置1 年洗脱期)、患病率。2. 通过 CCK-8 法研究 PA 对 DLD1 细胞增殖活性的影响;通过细胞划痕实验研究 PA对 DLD1 细胞迁移的影响;通过实时荧光定量 PCR 和蛋白质印迹法探究 PA 对 DLD1细胞的 EMT 相关指标 Snail、 E-cadherin、αSMA 表达水平的影响;利用 C57BL/6 野生型小鼠探究富含 PA 饮食对结肠炎小鼠结肠炎症因子 IL-1β、 IL-6、 TNF-α及 EMT相关指标 Snail、E-cadherin、αSMA 表达水平的影响。研究结果:第一部分:基于新农合数据研究北京市、海南省 UC 的流行趋势1.北京市 2014 年~2016 年新农合参保人群 UC 粗发病率由 0.58/10 万(95%CI:0.32/10 万-0.97/10 万)增长至 3.33/10 万(95%CI: 2.59/10 万-4.22/10 万), 2013年~2016 年 UC 粗患病率由 1.02/10 万(95%CI:0.67/10 万-1.50/10 万)增长至7.35/10 万(95%CI:6.22/10 万-8.62/10 万)。2.海南省 2014 年~2016 年新农合参保人群 UC 粗发病率由 0.04/10 万(95%CI:0.01/10 万-0.15/10 万)增长至 0.12/10 万(95%CI: 0.05/10 万-0.27/10 万); 2013年~2016 年 UC 粗患病率由 0.08/10 万(95%CI:0.02/10 万-0.22/10 万)增长至0.31/10 万(95%CI:0.17/10 万-0.51/10 万)。3. 2014 年~2016 年北京市 UC 标化发病率增长,但无线性趋势,海南省 UC 标化发病率线性增长,APC 为 89.7%;2013 年~2016 年北京市、海南省 UC 标化患病率呈线性增长趋势,APC 分别为 100.2%和 57.4%。 4. 2013 年~2016 年北京市 UC 门诊及住院平均就诊费用均有下降,海南省 UC 门诊及住院平均就诊费用则无显著变化趋势。第二部分:PA 对结肠炎症和上皮间质转化的影响初探1.0.2mM 及以上浓度 PA 处理 DLD1 细胞 24h 显著抑制细胞增殖活性(p<0.01),且该抑制作用具有浓度和时间依赖性。2.0.1、 0.2、 0.3mM PA 处理 DLD1 细胞 6、 12、 24h 存在抑制细胞迁移能力的趋势(p>0.05),且随 PA 浓度升高细胞呈迁移能力减弱趋势。3.0.2mM PA 处理 DLD1 细胞 24h 显著提高 Snail 的 mRNA 水平(p<0.05)、降低 Ecadherin 和αSMA 的 mRNA 水平(p<0.01)和蛋白表达量。4.PA+DSS 组小鼠的体重、 DAI 评分及结肠长度均与 DSS 组无统计学差异(p>0.05);PA+DSS 组小鼠的结肠病理评分及炎症因子 IL-1β、IL-6、TNFα mRNA 水平与 DSS组未见显著差异(p>0.05)。5.PA+DSS 组小鼠的 Snail mRNA 水平较 DSS 组小鼠显著增高(p<0.05), E-cadherin mRNA 水平较 NC 组和 DSS 组存在下降趋势(p>0.05), PA+DSS 组和 DSS 组小鼠的αSMA mRNA 水平无明显差异(p>0.05),均较 NC 组升高(p<0.05)。结论:北京市、海南省农村地区 UC 的发病率、患病率均逐年增长,提示北京市、海南省的 UC 疾病负担逐渐加重,需要加大对环境危险因素的防控力度。而 PA 抑制结肠上皮细胞的增殖活性及迁移能力,体内及体外实验均提示 PA 参与结肠 EMT 的调控,未来应该进一步研究不同炎症背景下 PA 对结肠 EMT 的影响及机制,以期为制定相应防控政策以及发现治疗靶点提供支持。
论文文摘(外文):
Objective: Ulcerative colitis (UC) is an idiopathic chronic disease that causes inflammation of the digestive tract. It brings a heavy burden on society and economy. There is a large rural population in our country, and the diet of rural residents is gradually westernized. Prevention and control of environmental risk factors has become an important mission. However, there is a lack of epidemiological data in rural areas, and the risk of high-fat components in the westernized diet for UC is controversial. This study described the incidence, prevalence and epidemiological trend of UC based on the New Rural Cooperative Medical System (NRCMS) data in Beijing and Hainan Province from 2013 to 2016. Then explored the effect of the saturated fatty acid palmitic acid (PA) on colonic inflammation and epithelial-to-mesenchymal transition (EMT). Our study aims to provide evidence for further assessment of the disease burden and the policy making of prevention and control of environmental risk facktors in our country. Method: 1. Data source was NRCMS database of Beijing and Hainan Province from 2013 to 2016. The target patients were extracted according to the formulated keywords. The gender, sex and date of treatment were extracted to estimate the incidence, prevalence. 2. The effect of PA on the proliferation ability of DLD1 cells was measured by CCK-8; the effect of PA on the migration ability of DLD1 cells was studied by cell wound scratch assay; the effect of PA on EMT of on DLD1 cells was explored by measuring the expression level of Snail, E-cadherin and αSMA; using C57BL/6 wild-type mice to explore the effect of PA-rich diet on the expression level of colonic inflammatory factors IL-1β, IL-6, TNF-α and EMT molecule Snail, E-cadherin and αSMA. Result: 1. Epidemiological trend of UC in Beijing and Hainan Province based on the NRCMS database.(1) In Beijing, the crude incidence of UC increased from 0.58/100,000 (95%CI: 0.32/100,000-0.97/100,000) to 3.33/100,000 (95%CI: 2.59/100,000-4.22/100,000) from 2014 to 2016; the cr ude prevalence of UC increased from 1.02/100,000 (95%CI: 0.67/100,000 -1.50/100,000) to 7.35/100,000 (95%CI: 6.22/100,000-8.62/100,000) from 2013 to 2016. (2) In Hainan Province, the crude incidence of UC increased from 0.04/100,000 (95%CI: 0.01/100,000-0.15/100,000) to 0.12/100,000 (95% CI: 0.05/100,000-0.27/100,000) from 2014 to 2016; the crude prevalence of UC increased from 0.08/100,000 (95%CI: 0.02/100,000-0.22/100,000) to 0.31/100,000 (95%CI: 0.17/100,000-0.51/100,000) from 2013 to 2016,.(3) From 2014 to 2016, the age-standardized incidence of UC in Hainan Province increased linearly and the APC was 89.7%; from 2013 to 2016, the age-standardized prevalence of UC increased linearly, with APCs of 100.2% and 57.4%, respectively. (4) From 2013 to 2016, the average cost of UC outpatients and inpatients in Beijing decreased, while the average cost of UC outpatients and inpatients in Hainan Province showed no significant trend. 2. A preliminary study on the effect of PA on colonic inflammation and epithelial-mesenchymal transition(1) 0.2mM and above PA treatment for 24h significantly inhibited proliferation activity of DLD1 cells (p<0.01), and the inhibitory effect was concentration- and time-dependent.(2) DLD1 cells treated with 0.1, 0.2, 0.3 mM PA for 6, 12 , and 24h tended to inhibit the cell migration ability (p>0.05), and the migration ability of the cells decreased with the increase of PA concentration.(3) DLD1 cells treated with 0.2 mM PA for 24h significantly increased the mRNA level of Snail (p < 0.05), and decreased the mRNA level (p < 0.01) and protein expression of E-cadherin and αSMA.(4) There was no significant difference between the DSS group and the PA+DSS group in the colonic pathological scores and the inflammatory factors IL-1β, IL- 6, TNFα mRNA level (p>0.05).(5) The level of Snail mRNA in the PA+DSS group was significantly higher than that in the DSS group (p<0.05), and the level of E -cadherin mRNA showed a downward trend compared with the NC group and the DSS group (p>0.05). There was no significant difference in the αSMA mRNA level between the PA+DSS group and the DSS group colonic tissue (p>0.05). Conclusion: The incidence and prevalence of UC in rural areas of Beijing and Hainan Province have increased from 2013 to 2016, suggesting t hat the burden of UC in Beijing and Hainan Province is gradually increasing, so it is necessary to strengthen the prevention and control of environmental risk factors. PA inhibits the proliferation and m igration ability of colonic epithelial cells. Both in vivo and in vitro experiments suggest that PA is involved in the regulation of colon EMT. In the future, the effect and mechanism of PA on colonic EMT under different inflammation backgrounds should be further studied in order to formulate corresponding p revention and control policies as well as ssupport for the discovery of therapeutic targets.
开放日期:

 2022-06-02    

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