白细胞介素-1和白细胞介素-10基因多态性与脓毒症发病的相关性研究  

The associations of the single nucleotide polymorphisms on interleukin-1 and interleukin-10 gene promoter with sepsis in surgical patients

作　　者：于宝军[1] 唐星明[1] 李志宇[1] 乔安意[1] 黎介寿[1] 

机构地区：[1]南京军区南京总医院解放军普通外科研究所,江苏南京210002

出　　处：《医学研究生学报》2007年第2期116-119,共4页Journal of Medical Postgraduates

基　　金：国家自然科学基金资助项目(批准号:30471674);江苏省六大人才高峰基金资助项目(批准号:06-B-074)

摘　　要：目的:探讨脓毒症患者白细胞介素-1(IL-1)和IL-10基因单核苷酸多态性(SNP)的频率分布以及与脓毒症易感性的相关性,观察不同多态性基因型对细胞因子表达的影响。方法:选择2001年10月至2004年12月在该院普通外科住院的181例患者,分为脓毒症组(100例)和全身炎症反应综合症(SIRS)组(81例),以150例健康人群作为对照组。取外周血白细胞提取基因组DNA,用PCR扩增限制性内切酶长度多态性的方法,检测IL-1基因上+3 953T、IL-10基因上-592A和-1082A,共3个SNP。在诊断为SIRS或脓毒症24 h内取外周血单个核细胞提取总RNA,用RT-PCR法检测IL-1和IL-10 mRNA的表达;同时取血浆用ELISA法检测细胞因子蛋白表达。结果:SIRS组和脓毒症组中,+3 953T、-592A出现的频率明显高于对照组。在脓毒症早期,IL-1 mRNA及蛋白的表达水平在+3 953C/T组明显高于C/C组;而IL-10两个SNP对脓毒症早期的IL-10表达水平,无明显的影响作用。结论:该研究显示,IL-1及IL-10基因上SNP差异可能是脓毒症患者易感的原因之一。在脓毒症发生机制中,有促炎介质和抑炎因子的共同参与,其表达水平与SIRS及脓毒症的发生和严重程度相关。Objective： To investigate the associations of the single nucleotide polymorphisms （SNP） on interleukin-1 （IL-1）, interleukin-10（IL-10） gene promoter with the expression of the cytokines and the complication with SIRS or sepsis in surgical patients. Methods： 181 patients with diagnosis of SIRS （81patients） or sepsis（100 patients） and 150 healthy subjects as controls were involved in this study. After genomic DNA were extracted from whole blood specimen, the SNP genotypes of IL-1 ＋ 3 953C/T, IL-10 -592 C/A, and -1 082G/A were examined by restriction fragment length polymorphism PCR （PCR-RFLP）. The expressions of the cytokines mRNA of peripheral blood mononuclear cell （PBMC） in parts of the patients during 24 hours after the dignosis of sepsis or SIRS, and with at least one genotype of SNP, were detected by RT-PCR, meanwhile the plasma levels of IL-1 and IL-10 were determined by ELISA. Results：The rates of IL-1 ＋3 953C/T, IL-10 -592A/A, genotypes and alleles in patients with sepsis were significantly higher than that of patients with SIRS and healthy volunteers. The expression of IL-1 mRNA and IL-1 levels were much higher in patients with ＋ 3 953C/T than those with ＋3953C/C genotype. IL-10 mRNA and protein were not influenced by the two SNP in IL-10 gene according to our data. Conclusion：The IL-1 ＋ 3 953T and the -592A -allele were associated with the higher risk of sepsis. The ＋ 3953T could increase IL-1 mRNA and protein expression. Both single nucle- otide polymorphisms of proinflammatory and anti-inflammatory cytokines may play important roles in the mechanism of the onset of sepsis.

关 键 词：白细胞介素-1 白细胞介素-10 单核苷酸多态性 脓毒症 

分 类 号：R631.2[医药卫生—外科学]