摘要
目的探讨Toll-样受体4(TLR4)和肠道菌群在原发性肝癌进展中动态变化情况,并分析其与预后之间的关系。方法选取100例慢性乙肝患者、80例肝硬化合并乙型肝炎患者和60例肝癌合并乙型肝炎患者作为研究对象,并分别命名为乙型肝炎组、肝硬化组和肝癌组,另选取年龄及性别与其匹配的100名健康体检者作为对照组。采用流式细胞术检测各组外周血单核细胞表面TLR4表达情况,收集各组新鲜粪便,并检测其肠道菌群的分布,并分析两者之间的关系。比较各组外周血单核细胞表面TLR4表达和肠道菌群分布差异,并分析其与肝癌患者预后之间的关系。结果对照组、乙型肝炎组、肝硬化组和肝癌组外周血CD14+TLR4+单核细胞阳性率分别为(34.92±4.79)%、(41.92±7.46)%、(49.21±8.83)%和(57.62±10.58)%,4组比较差异有统计学意义(F=78.624,P<0.01);双歧杆菌含量分别为(10.73±2.91)lg CFU/g、(8.15±2.04)lg CFU/g、(6.33±1.32)lg CFU/g和(5.21±0.87)lg CFU/g,4组比较差异有统计学意义(F=15.932,P<0.01);肠球菌含量分别为(4.91±0.78)log CFU/g、(6.44±1.29)log CFU/g、(8.11±2.08)log CFU/g和(10.21±2.77)log CFU/g,4组比较差异有统计学意义(F=12.372,P<0.01)。经Pearson相关分析得知,单核细胞表面TLR4表达与乳酸杆菌和双歧杆菌呈负相关(P<0.05),其相关系数分别为-0.643和-0.672;与肠球菌和大肠埃希菌呈正相关(P<0.05),其相关系数分别为0.771和0.734。随访1年,60例肝癌患者中,18例复发,15例死亡。复发者和未复发者外周血CD14+TLR4+单核细胞阳性率分别为(59.32±9.17)%和(55.21±5.23)%,两者比较差异有统计学意义(t=2.200,P=0.032);死亡者与生存者外周血CD14+TLR4+单核细胞阳性率分别为(61.04±10.23)%和(53.29±8.11)%,两者比较差异有统计学意义(t=2.998,P=0.004)。与未复发者和生存者比较,复发者和死亡者双歧杆菌和乳酸杆菌含量明显减少,但肠球菌和大肠埃希菌含量则明显升高,差异有统计学意义(P<0.05)。结论TLR4可促进HBV进展为肝癌,与肠道菌群变化明显相关,两者在肝癌预后监测中有一定价值。
Objective To investigate the dynamic changes of Toll-like receptor 4(TLR4)and intestinal flora in the progression of primary liver cancer,and to analyze their relationship with prognosis.Methods 100 patients with chronic hepatitis B(HBV),80 patients with cirrhosis and HBV,and 60 patients with hepatocellular carcinoma and HBV were enrolled as subjects.They were named HBV group,cirrhosis group and liver cancer group,and matched with age and gender.One hundred healthy subjects were used as a control group.The expression of TLR4 on the surface of peripheral blood mononuclear cells was detected by flow cytometry.Fresh feces were collected from each group,and the distribution of intestinal flora was detected.The relationship between the two groups was analyzed.The expression of TLR4 and the distribution of intestinal flora in peripheral blood mononuclear cells of each group were compared,and the relationship between the expression of TLR4 and the prognosis of liver cancer patients was analyzed.Results The positive rates of CD14+TLR4+monocytes in the peripheral blood of the control group,HBV group,liver cirrhosis group and liver cancer group were gradually increased,which were(34.92±4.79)%,(41.92±7.46)%,(49.21±8.83)%,and(57.62±10.58)%respectively,the difference between the four groups was statistically significant(F=78.624,P=0.000).The content of bifidobacteria in the control group,HBV group,liver cirrhosis group and liver cancer group decreased sequentially as(10.73±2.91)log CFU/g,(8.15±2.04)log CFU/g,(6.33±1.32)log CFU/g,and(5.21±0.87)log CFU/g,the difference between the four groups was statistically significant(F=15.932,P=0.000);the content of enterococci in the control group,HBV group,cirrhosis group and liver cancer group increased in turn,respectively(4.91±0.78)log CFU/g,(6.44±1.29)log CFU/g,(8.11±2.08)log CFU/g and(10.21±2.77)log CFU/g,the difference between the four groups was statistically significant(F=12.372,P=0.000).According to Pearson correlation analysis,the expression of TLR4 on the surface of monocytes was negatively correlated with Lactobacillus and Bifidobacteria(P<0.05),and the correlation coefficients were-0.643 and-0.672 respectively.It was positively correlated with Enterococcus and Escherichia coli.(P<0.05),the correlation coefficients were 0.771 and 0.734 respectively.During the follow-up of 1 year,18 of the 60 patients with liver cancer recurred and 15 died.The positive rates of CD14+TLR4+monocytes in peripheral blood in relapsed and non-relapsed patients were(59.32±9.17)%and(55.21±5.23)%,respectively,and the difference was statistically significant(t=2.200,P=0.032).The positive rates of CD14+TLR4+monocytes in peripheral blood of the deceased and survivors were(61.04±10.23)%and(53.29±8.11)%,respectively,and the difference was statistically significant(t=2.998,P=0.004).Compared with non-recurring and survivors,the content of bifidobacteria and lactobacilli in relapsed and deceased patients was significantly reduced,but the contents of Enterococcus and Escherichia coli were significantly increased,the difference was statistically significant(P<0.05).Conclusion TLR4 can promote the progression of HBV to liver cancer,which is significantly correlated with the changes of intestinal flora.Both of them have certain value in the prognosis monitoring of liver cancer.
作者
王雨
许达峰
周开伦
武金才
丁驿超
古海强
谢明微
林明花
WANG Yu;XU Da-feng;ZHOU Kai-lun;WU Jin-cai;DING Yi-chao;GU Hai-qiang;XIE Ming-wei;LIN Ming-hua(Department of Hepatobiliary Surgery,Hainan Provincial People′s Hospital,Haikou 570031,China)
出处
《肝脏》
2020年第3期273-276,共4页
Chinese Hepatology
