肝细胞性肝癌TACE后血清内毒素、TOLL样受体4和肠道微生态改变的实验观察

Experimental observation on the changes of serum lipopolysaccharides,Toll-like receptor 4 and intestinal microecology in hepatocellular carcinoma after TACE

目的:观察肝细胞性肝癌病人经动脉化疗栓塞术(TACE)后血清内毒素(lipopolysaccharides,LPS)、TOLL样受体4(Toll-like receptor 4,TLR4)及肠道微生态的改变。方法:收集初诊为原发性肝癌病人11例,均采取常规TACE治疗,治疗前后不加服任何影响肠道微生态变化的药物制剂,观察此组病人术前1 d、术后1周及术后1个月病人LPS、TLR4含量以及肠道菌群变化情况。结果:病人术前1 d、术后1周、术后1个月时血清内LPS、TLR4含量差异均有统计学意义(P<0.01),Bonferroni两两比较分析发现,LPS含量术前1 d低于术后1周及术后1个月,TLR4含量术后1个月低于术前1 d及术后1周,差异均有统计学意义(P<0.05~P<0.01)。病人术后1周时肠道菌群丰度稍升高,而随后1个月其丰度下降,且低于术前1 d的水平,通过单因素方差分析显示拟杆菌、毛螺菌等益生菌丰度高于术前1 d及术后1周,且链球菌、乳杆菌等潜在致病菌属低于术前1 d及术后1周,且3组比较差异有统计学意义(P<0.05)。结论:原发性肝癌行TACE治疗后,通过肝肠轴能显著促进肠道微生态平衡,同时肠道微生物稳态不仅能作为肝癌TACE术后评价的指标,还能促进肝癌预后。

Objective:To observe the changes of serum lipopolysaccharides(LPS),Toll-like receptor 4(TLR4)and intestinal microecology in patients with hepatocellular carcinoma(HCC)after transcatheter arterial chemoembolization(TACE).Methods:Eleven patients with HCC were treated with TACE,and no drug was added to affect the intestinal microecological changes before and after treatment.The serum levels of LPS and TLR4 and intestinal microecological changes were obserevd before 1 day of operation and after 1 week and 1 month of operation.Results:The differences of the serum levels of LPS and TLR4 in patients among before 1 day of operation and after 1 week and 1 month of operation were statistically significant(P<0.01).The results of Bonferroni′s pairwise comparative analysis showed that the level of LPS before 1 day of operation was lower than that after 1 week and 1 month of operation,and the level of TLR4 after 1 month of operation was lower than that before 1 day of operation and after 1 week of operation(P<0.05 to P<0.01).The results of ACE index difference analysis showed that the abundance of intestinal flora increased slightly at 1 week after operation,and then decreased in the following 1 month,which was lower than that before 1 day of operation.The results of One-way ANOVA analysis showed that the abundance of probiotic bacteria such as Bacteroides and Lachnospira were higher than that before 1 day of operation and after 1 week of operation,the abundance of Streptococcus and Lactobacillus were lower than that before 1 day of operation and after 1 week of operation,and the differences of which among three groups were statistically significant(P<0.05).Conclusions:After the treatment of primary liver cancer with TACE,the intestinal microecological balance can be significantly promoted through the hepato-intestinal axis.Meanwhile,the intestinal microbial homeostasis can not only be used as an indicator for the evaluation of liver cancer after TACE,but also promote the prognosis of liver cancer.