【作者】 张志强；

【导师】 王沁；

【作者基本信息】 兰州大学 ， 内科学， 2010， 硕士

【摘要】 目的：肠易激综合征(Irritable Bowel Syndrome, IBS)是一种常见的肠道功能紊乱性疾病,以反复发作性腹痛、腹部不适为主要特征同时伴排便习惯改变,发病机制目前尚未完全阐明,遗传因素可改变个体对IBS的易感性,基因多态性在IBS发病过程中起着重要作用,本课题研究内脏感知异常和辣椒素受体(Transient Receptor Potential Vanilloid-1.TRPV1)基因多态性与IBS的关系。方法：以罗马III诊断标准纳入病例73例,正常对照65例,(1)采用聚合酶链反应(Polymerase Chain Reaction, PCR)限制性酶切片段多态性(Restriction Fragment Length Polymorphism, RFLP)方法对研究对象进行TRPV1的基因型和等位基因分析,并对突变的纯合基因型进行直接测序,比较两组之间的差别；(2)采用PC Polygraf ID高分辨率多通道胃肠功能检测仪和8通道带气囊灌注式测压管检测31例IBS患者和16例正常对照组直肠肛管感觉,记录初始感觉阈值(First Sensation Volume, FSV)、排便阈值(Defecating Sensation Volume,DSV)、排便窘迫阈值(Maximum Tolerable Volume, MTV)和最大容量感觉阈值(Painful Sensation Volume, PSV)。结果：测出3种TRPV1基因型：CC型、CT型、TT型。IBS组CC基因型的频率明显高于对照组(25例VS 10例,χ2=6.858,P=0.032),等位基因C的频率IBS组明显高于正常对照组(93 VS 67,χ2=4.174,P=0.041),IBS组与对照组之间有统计学差异(P<0.05)；TT基因型的测序结果在NCBI网站进行BLAST比对发现在-116位为T,与预期结果相符合；与对照组相比,IBS组个体的FSV(24.71ml±5.52mlvs 32.86ml±5.67ml, P=0.019); DSV (64.29ml±9.75ml vs 80.01ml±14.41 ml, P=0.03); MTV (84.57ml±9.07ml vs 133.57ml±9.88ml, P<0.001); PSV (143.57ml±9.89ml vs 231.42ml±12.49ml,P<0.001)明显低于正常对照组(P<0.05)结论：IBS患者存在内脏高敏感性,TRPV1基因多态性可能影响个体对IBS的遗传易感性以及IBS患者的内脏高敏感性,TRPV1有望成为治疗IBS的一个作用靶点。更多还原

【Abstract】 Obective:Irritable bowel syndrome is one of the most common functional gastrointestinal disorders which the pathogenesis is not yet clear. It is characterized by chronic and recurrent abdominal pain or discomfort along with altered bowel function. Genetic factors alter the susceptibility to IBS of individuals. Our objective is to investigate the relationship between transient receptor potential vanilloid-1 (TRPV1) gene polymorphism and irritable bowel syndrome (IBS) and its visceral hyperalgesia (VHL).Methods:Polymerase chain reaction(PCR)-Restriction fragment length polymorphism (RFLP) and direct sequence was used to comparatively analyze the polymorphism of TRPV1 gene with IBS (n=73) fulfilling Rome III criteria and healthy control(n=65). PC Polygraf ID gastrointestinal function testing equipment and 8-chaanel perfusion with a balloon-type piezometer was Used to test the IBS (n=31) and healthy controls’(n=16)anorectal feeling and the first sensation volume(FSV), defecating sensation volume(DSV), maximum tolerable volum (MTV) and painful sensation volume(PSV) was recorded.Result:We found three genotypes in the case and controls that they were CC, CT and TT. The frequencies of CC genotype and C allele in IBS patients were significantly higher than those in the controls (genotype:X2=6.858,P=0.032; allele:X2=4.174, P=0.041). Significant difference was found in TRPV1 gene polymorphism between IBS and control (P<0.05). FSV(24.71ml±5.52ml vs 32.86ml±5.67ml P=0.019), DSV(64.29ml±9.75ml vs 80.01 ml±14.41 ml,P=0.03), MTV (84.57ml±9.07ml vs 133.57ml±9.88ml,P<0.001), PSV (143.57ml±9.89ml vs 231.42ml±12.49ml,P<0.001) of IBS are much lower than healthy control(P<0.05).Conclusion:VHL is one of the pathophysiology characters of IBS and play an important role in IBS. Polymorphism of TRPV1 gene is associated with IBS. TRPV1 is expected to be a novel therapeutic target for IBS.更多还原