慢性乙型肝炎患者炎症因子表达水平及IL-23/IL-17信号通路的活性变化

Changes of expression of inflammatory factors and activity of IL-23/IL-17 signaling pathway in patients with chronic hepatitis B

目的探讨慢性乙型肝炎患者炎症因子表达及白介素-23(IL-23)/白介素-17(IL-17)信号通路的活性变化。方法选择2017年3月-2019年3月华中科技大学同济医学院附属武汉中心医院收治的慢性乙型肝炎患者196例,按照病情不同程度分为轻度组41例、中度组87例、重度组68例,随机选择100名健康体检者作为对照组。采用放射免疫法测定肝纤维化指标透明质酸(HA)、层黏蛋白(LN)、Ⅲ型前胶原(P-Ⅲ)和Ⅳ型胶原(Ⅳ-C)含量;采用酶联免疫吸附法(ELISA法)测定炎症因子高迁移率族蛋白-1(HMGB-1)、白介素-10(IL-10)和肿瘤坏死因子-α(TNF-α)含量;采用qRT-PCR法检测外周血RORγt mRNA表达,ELISA法检测IL-17和IL-23表达。结果各组肝纤维化指标比较差异有统计学意义(P<0.05),轻度组、中度组和重度组HA、LN、P-Ⅲ和Ⅳ-C水平均高于对照组,且中度组和重度组高于轻度组,重度组高于中度组(P<0.05);各组炎症因子HMGB-1、IL-10和TNF-α水平比较差异有统计学意义(P<0.05),轻度组、中度组和重度组均高于对照组,中度组和重度组高于轻度组,重度组高于中度组(P<0.05);各组RORγt mRNA表达、IL-17和IL-23水平比较差异有统计学意义(P<0.05),轻度组、中度组和重度组高于对照组,中度组和重度组高于轻度组,重度组高于中度组(P<0.05)。结论慢性乙型肝炎患者炎症因子HMGB-1、IL-10和TNF-α高表达,且Th17表达、RORγt mRNA表达及IL-17和IL-23表达升高,推测炎症因子和IL-23/IL-17信号通路的活性可能是维持乙型肝炎病毒持续性感染的一个机制。

OBJECTIVE To explore the changes of expression of inflammatory factors and activity of interleukin-23(IL-23)/interleukin-17(IL-17)signaling pathway in patients with chronic hepatitis B.METHODS Totally 196 patients with chronic hepatitis B who were treated in Wuhan Central Hospital,Tongji Medical College,Huazhong University of Science and Technology from Mar 2017 to Mar 2019 were enrolled in the study and divided into the mild group with 41 cases,the moderate group with 87 cases and the severe group with 68 cases according to the severity of disease,meanwhile,100 healthy people who received physical examination were randomly chosen as the control group.The contents of liver fibrosis indexes hyaluronic acid(HA),laminin(LN),typeⅢprocollagen(P-Ⅲ),and type IV collagen(IV-C)were detected by using radioimmunoassay,the contents of inflammatory factors high mobility group protein-1(HMGB-1),interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)were determined by means of enzyme-linked immunosorbent assay(ELISA),the expression of peripheral blood RORγt mRNA was detected with the use of qRT-PCR,and the levels of serum interleukin-17(IL-17)and interleukin-23(IL-23)were detected by using ELISA.RESULTS There were significant differences in the liver fibrosis indexes among the four groups(P<0.05),the levels of HA,LN,P-ⅢandⅣ-C of the mild group,the moderate group and the severe group were significantly higher than those of the control group,the levels of above indexes of the moderate group and the severe group were significantly higher than those of the mild group,and the levels of above indexes of the severe group were significantly higher than those of the moderate group(P<0.05).There were significant differences in the levels of inflammatory factors HMGB-1,IL-10 and TNF-αamong the four groups(P<0.05),the levels of above indexes of the mild group,the moderate group and the severe group were significantly higher than those of the control group,the levels of above indexes of the moderate group and the severe group were significantly higher than those of the mild group,and the levels of above indexes of the severe group were significantly higher than those of the moderate group(P<0.05).There were significant differences in the expression of RORγt mRNA and levels of IL-17 and IL-23 among the four groups(P<0.05),the levels of above indexes of the mild group,the moderate group and the severe group were significantly higher than those of the control group,the levels of above indexes of the moderate group and the severe group were significantly higher than those of the mild group,and the levels of above indexes of the severe group were significantly higher than those of the moderate group(P<0.05).CONCLUSION The patients with chronic hepatitis B show high expression of inflammatory factors HMGB-1,IL-10 and TNF-αand the rise of levels of Th17,RORγt mRNA,IL-17 and IL-23,indicating that the inflammatory factors and activity of IL-23/IL-17 signaling pathway may be a mechanism for maintaining the persistent infection with hepatitis B virus.