非酒精性脂肪性肝病病人肠道微生态系统变化及其对机体炎症反应的影响机制

Effects of the change of intestinal microecosystem on inflammatory reaction in patients with non-alcoholic fatty liver disease and its mechanism

目的:探讨非酒精性脂肪性肝病(NAFLD)病人的肠道微生态系统变化对机体炎症反应的影响机制。方法:选择2018年07月至2019年07月入新疆医科大学第二附属医院首次确诊60例NAFLD病人作为观察组和60例健康体检者作为对照组。采用肠道微生物多样性分析技术检测观察组治疗前后和对照组的肠道菌群种类和数量,ELISA法检测炎症因子IL-6和TGF-β水平,Western blot法检测Toll样受体(TLR)-4和NF-κB(p65)蛋白水平。结果:与治疗前比较,观察组治疗后BMI、LDL-C与总胆红素(CHO)显著降低(P<0.05)。治疗前与对照组比较,观察组肠道菌群以大肠埃希菌、金黄色葡萄球菌、肠球菌为主的致病菌显著增加,而以乳酸杆菌、罗氏菌为主的益生菌显著减少(P<0.05)。观察组治疗后与治疗前比较,致病菌数量减少,益生菌增加(P<0.05)。治疗前与对照组比较,观察组血清IL-6、TGF-β、TLR-4和NF-κB(p65)蛋白水平明显升高(P<0.05)。观察组治疗后与治疗前比较,血清IL-6、TGF-β、TLR-4和NF-κB(p65)蛋白水平显著降低(P<0.05)。结论:NAFLD病人肠道微生态系统出现致病菌增多,益生菌减少,并导致机体炎症相关因子表达的升高,可能是NAFLD发生和病情进展的重要机制之一。

Objective:To analyze the effect of the change of intestinal microecosystem on inflammatory reaction in patients with non-alcoholic fatty liver disease(NAFLD)and to explore its mechanism.Methods:A total of 60 patients diagnosed to NAFLD were enrolled into observation group from July 2018 to July 2019.And the 60 healthy examinees were enrolled into in control group.The kinds and quantities of intestinal flora of two groups were detected by intestinal microbial diversity analysis at pre-and post-therapy,respectively.The inflammatory factors levels of IL-6 and TGF-βwere detected by ELISA.And the protein levels of Toll-like receptor(TLR)-4 and NF-κB(p65)were detected by Western blot.Results:The levels of BMI,LDL-C and CHO of observation group at post-therapy were obviously lower than at pre-therapy(P<0.05).The pathogenic bacteria of Escherichia coli,Staphylococcus aureus and Enterococcus of observation group at pre-therapy were higher than control group(P<0.05),but the probiotics of Lactobacillus and Rochella of observation group at pre-therapy were lower than control group(P<0.05).Compared to pre-therapy,the quantities of pathogenic bacteria of observation group at post-therapy were obviously lower and the probiotics were higher(P<0.05).The serum levels of IL-6、TGF-β、TLR-4 and NF-κB(p65)of observation group at pre-therapy were higher than control group(P<0.05).Compared to pre-therapy,the serum levels of IL-6、TGF-β、TLR-4 and NF-κB(p65)of observation group at post-therapy were obviously lower(P<0.05).Conclusion:The quantities of pathogenic bacteria of intestinal microecosystem in patients with NAFLD are increasing,but the probiotics are decreasing,which can up-regulate the inflammatory factor levels.It may be one of important mechanisms to the occurrence and progression of NAFLD.