【摘要】 目的 探讨NF-κB在重症急性胰腺炎小鼠肠黏膜屏障功能损伤中的调控机制。 方法 36只BALB/C小鼠随机分为对照组、模型组、NF-κB干预组，每组12只。18 h后处死小鼠，比较各组的腹腔内大体改变、肠黏膜病理改变，肠道通透性的变化及血清细胞因子水平，肠上皮紧密连接蛋白occludin的表达。 结果 模型组小鼠腹腔内呈明显炎症反应，肠管水肿，肠黏膜水肿，肠道通透性显著增高，NF-κB特异性阻断剂能降低肠道损伤，改善肠黏膜水肿，上调肠上皮紧密连接蛋白occludin的表达，显著降低肠道通透性，降低细胞因子水平。 结论 NF-κB阻断剂能够通过选择性的抑制NF-κB活性，改善受损的肠屏障功能。这一作用通过上调肠上皮紧密连接蛋白occludin的水平而实现。【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.