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为探讨慢性乙型肝炎(chronic hepatitis B,CHB)患者及抗病毒治疗后患者IL-23/IL-17信号通路活性变化,本研究以2011年10月至2015年8月昆明医科大学第一附属医院感染科门诊及住院部收治的HBeAg阳性CHB患者111例作为观察组,并且选取相同时间段体检健康者22例作为对照组。治疗48周时根据HBeAg变化将其分为HBeAg阳性组、HBeAg阴性组和HBeAg/HBeAb血清学转换组。采用全自动生化分析仪检测丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate transaminase,AST)、总胆红素(total bilirubin,TBIL)水平;采用RT-PCR法测定患者血清HBV-DNA载量;采用流式细胞术检测外周血Th17细胞表达率;应用qRT-PCR法测定外周血维甲酸相关核孤儿受体(retinoid-related orphan nuclear receptorγt,RORγt)mRNA表达水平;采用ELISA法检测IL-17与IL-23水平。研究结果显示与对照组相比,CHB组Th17、RORγt、IL-17和IL-23水平显著增加(P<0.05);与治疗前相比,治疗48周后Th17、RORγt、IL-17和IL-23水平显著下降(P<0.05)。治疗48周时ALT复常率、HBV-DNA检测不到率和HBeAg血清学转换率分别是94.6%、80.2%和18.0%。HBeAg/HBeAb血清学转换组Th17、RORγt、IL-17和IL-23水平显著低于HBeAg阳性组(P<0.05)。综上,本研究发现IL-23/IL-17信号通路参与了CHB患者的炎症反应过程,抗病毒治疗可以降低Th17、RORγt、IL-17和IL-23水平,进而通过IL-23/IL-17信号通路有限度地控制肝脏病程进展。
To investigate the changes of IL-23 / IL-17 signaling pathway in patients with chronic hepatitis B (CHB) and after antiviral therapy, this study was conducted from October 2011 to August 2015 in Kunming Medical University 111 cases of HBeAg positive CHB patients admitted to Hospital Infectious Diseases Clinic and Inpatient Department were selected as the observation group, and 22 healthy subjects were selected as the control group in the same time period. After 48 weeks of treatment, they were divided into HBeAg positive group, HBeAg negative group and HBeAg / HBeAb seroconversion group according to the change of HBeAg. The levels of alanine aminotransferase (ALT), aspartate transaminase (AST) and total bilirubin (TBIL) were detected by automatic biochemical analyzer. Method to measure the serum HBV-DNA load in patients. The expression of Th17 cells in peripheral blood was detected by flow cytometry. The mRNA expression of retinoid-related orphan nuclear receptorγt (RORγt) in peripheral blood was measured by qRT-PCR The levels of IL-17 and IL-23 were detected by ELISA. The results showed that compared with the control group, the levels of Th17, RORγt, IL-17 and IL-23 in CHB group were significantly increased (P <0.05); Th17, RORγt, IL-17 and IL -23 levels decreased significantly (P <0.05). At 48 weeks of treatment, ALT normalization rate, undetectable HBV-DNA and HBeAg seroconversion rates were 94.6%, 80.2% and 18.0%, respectively. The levels of Th17, RORγt, IL-17 and IL-23 in HBeAg / HBeAb seroconversion group were significantly lower than those in HBeAg-positive group (P <0.05). In summary, IL-23 / IL-17 signaling pathway is involved in the inflammatory response in CHB patients. Antiviral treatment can reduce the levels of Th17, RORγt, IL-17 and IL-23, 17 signaling pathways have limited control of liver progression.