肝硬化超声影像特点与患者肠黏膜炎性因子和Th1/Th2变化的关联

The correlation between ultrasonographic features of liver cirrhosis and changes of intestinal inflammatory factors as well as Th1/Th2 in patients with liver cirrhosis

目的通过超声影像研究肠黏膜炎性因子是否改变肝硬化以及肝硬化患者外周血中CD+4细胞内Th1和Th2类细胞的平衡状态,研究Th1、Th2类细胞在肝硬化中的作用。方法选取36例患者作为研究对象,随机分为3组:健康对照组、代偿期组和失代偿期组,每组12例,肝硬化患者接受十二指肠活检。在肠标本中,通过形态学评估记录黏膜细胞凋亡和有丝分裂活性及其比值,并测量黏膜脂质过氧化产物。同时测定了肠屏障功能指标血浆内毒素浓度。采用流式细胞术(FACS)对Th1、Th2细胞失衡与肝硬化的发病关系进行分析。对3组患者进行血清Th1(IFN-γ)和Th2细胞因子白介素4(IL-4)、IL-13、IL-10、IL-6和肿瘤坏死因子-α(TNF-α)的测定。结果肝硬化患者血清内毒素水平明显高于健康对照组(P<0.001),而失代偿期内毒素较代偿期血症更高(P<0.05)。与健康对照组比较,代偿期和失代偿期组肠道黏膜有丝分裂计数显著降低(P<0.01),凋亡增加的趋势。与健康对照组比较,代偿期组和失代偿期组有丝分裂/凋亡率显著降低(P<0.05)。失代偿期肝硬化患者的肠道脂质过氧化与健康对照组和代偿期组比较显著增加(P<0.001)。代偿期肝硬化组、失代偿期肝硬化组IFN-γ、IL-13、IL-10水平高于对照组,IL-4水平低于对照组,差异有统计学意义(P<0.05)。结论即使在肝硬化早期,人类肝硬化也与肠黏膜增殖和增殖/凋亡率下降有关,并且在晚期肝病中,肠氧化应激增加。肝硬化血清IFN-γ水平升高,IL-13和IL-10升高,而IL-4水平降低。

Objective To investigate whether intestinal inflammatory factors can change the balance status of Th1 and Th2 cells in CD4+cells of patients with cirrhosis by means of ultrasound images,and to explore the role of Th1 and Th2 cells in cirrhosis.Methods Thirty-six patients with cirrhosis were randomly divided into three groups:health control group(group A),compensatory period group(group B)and decompensated period group(group C),with 12 cases in each group,and the patients with liver cirrhosis received duodenal biopsy.The intestinal specimens were collected,and apoptotic and mitotic activities and their ratio were evaluated by morphology,and lipid peroxidation products of mucosa were measured.Meanwhile,plasma endotoxin concentration was determined as an index of intestinal barrier function.Flow cytometry(FACS)was used to analyze the correlation between Th1 Th2 cell imbalance and cirrhosis.Moreover the serum levels of TH-1(IFN-gamma),TH-2 cytokines(IL-4,IL-13),IL-10,IL-6 and TNF-alpha were detected and compared among the three groups.Results The serum levels of endotoxin in patients with liver cirrhosis were significantly higher than those in healthy subjects(P<0.01),which in group C significantly higher than those in group B(P<0.05).As compared with those in health control group,the intestinal mucosal mitotic counts in group B and group C were significantly decreased(P<0.01).As compared with those in health control group,the mitosis/apoptosis rates in group B and group C were significantly decreased(P<0.01).Moreover the lipid peroxidation levels in group C were significantly increased,as compared with those in health control group and group A(P<0.05).The levels of IFN-γ,IL-13,IL-10 in group B and group C were significantly higher than those in health control group,however,the levels of IL-4 in group B and group C were significantly lower than those in health control group(P<0.05).Conclusion Even in the early stage of cirrhosis,human cirrhosis is related to the decrease of intestinal mucosal proliferation and proliferation/apoptosis rates,and intestinal oxidative stress in increased in advanced liver diseases.The serum levels of IFN-γ,IL-13 and IL-10 are increased,however the serum levels of IL-4 are decreased in patients with liver cirrhosis.