【摘要】 目的 探討NF-κB在重癥急性胰腺炎小鼠腸黏膜屏障功能損傷中的調控機制。 方法 36只BALB/C小鼠隨機分為對照組、模型組、NF-κB干預組，每組12只。18 h后處死小鼠，比較各組的腹腔內大體改變、腸黏膜病理改變，腸道通透性的變化及血清細胞因子水平，腸上皮緊密連接蛋白occludin的表達。 結果 模型組小鼠腹腔內呈明顯炎癥反應，腸管水腫，腸黏膜水腫，腸道通透性顯著增高，NF-κB特異性阻斷劑能降低腸道損傷，改善腸黏膜水腫，上調腸上皮緊密連接蛋白occludin的表達，顯著降低腸道通透性，降低細胞因子水平。 結論 NF-κB阻斷劑能夠通過選擇性的抑制NF-κB活性，改善受損的腸屏障功能。這一作用通過上調腸上皮緊密連接蛋白occludin的水平而實現。【Abstract】 Objective To investigate the roles of NF-κB in the intestinal mucosal barrier injury in mice with severe acute pancreatitis(SAP). Methods Thirty-six BALB/C mice were randomly assigned to normal control group, SAP model group and intervention group. Eighteen hours later, pathological intestinal villus changes, intestinal permeability, serum cytokines were evaluated in all three groups. Results In SAP model group, intestinal mucosa was found to be oedematous and intestinal permeability was markedly increased. NF-κB could ameliorate intestinal injury and mucosa edema, and improve intestinal permeability by upregulating occluding expression. Conclusion NF-κB could protect the function of intestinal mucosal barrier by inhibiting NF-κB activity, which suggests that NF-κB may play an intermediating role in SAP-induced intestinal failure through upregulating occluding expression.
ObjectiveTo explore the association of elongase of very long chain fatty acids family member 6 (ELOVL6) gene with increased risk of large-artery atherosclerosis stroke (LAA) in Han Chinese population in Chengdu.MethodsHan Chinese populations in Chengdu, Sichuan were chosen for this study using the case-control design between January 2015 and December 2017. The genotypes and haplotypes of six single nucleotides polymorphisms (SNPs) of ELOVL6 gene (rs3813825, rs17041272, rs4141123, rs9997926, rs6824447, and rs12504538) were analyzed in different genetic models in entire samples, and gene-enviromental interaction analyses were also carried out to get an insight of the risk factors for LAA. At the same time, we also analyzed the gene expression profile in peripheral blood mononuclear cells between groups.ResultsA total of 240 LAA cases and 211 healthy controls were enrolled in this study. All the enrolled subjects presented CC genotype of rs9997926, while the other five SNPs (rs3813825, rs17041272, rs4141123, rs6824447, and rs12504538) were genotyped successfully in all the enrolled subjects. rs17041272 polymorphism and TGTTG haplotype were significantly associated with LAA risk in studied population [CC/(CG+GG): odds ratio (OR)=0.640, 95% confidence interval (CI) (0.423, 0.968), P=0.034; TGTTG: OR=1.776, 95%CI (1.069, 2.951), P=0.024], and the interaction among rs17041272, rs6824447 SNPs and dyslipidemia increased susceptibility to LAA [OR=2.737, 95%CI (1.715, 4.368), P<0.001]. The ELOVL6 gene expression level was higher in LAA subjects (t=?3.167, P=0.003).ConclusionsELOVL6 gene is associated with LAA risk in Han nationality of Chinese population in Chengdu, and the interaction of gene-environmental risk factors could be of great importance in pathophysiology of LAA.