替比夫定对慢性HBV感染孕妇细胞因子的表达影响研究

发布时间：2018-08-17 12:43

【摘要】：目的：本研究拟通过测定不同表型慢性乙型肝炎病毒(hepatitis B virus，HBV)感染孕妇HBV相关血清细胞因子/趋化因子水平，，了解HBV感染孕妇的免疫状态；评估替比夫定治疗对孕妇免疫的影响，进一步从免疫层面探讨替比夫定治疗阻断母婴传播的机制。方法：收集2012年1月至2013年12月检测乙型肝炎表面抗原(hepatitis B surfaceantigen，HbsAg)及乙型肝炎e抗原(hepatitis B e antigen，HbeAg)均为阳性且HBVDNA≥106IU/mL的慢性HBV感染孕妇血清标本，替比夫定组孕28~32周开始服用替比夫定，对照组孕期未予治疗。主要试验方法有：①蛋白质芯片试验：3例替比夫定组孕妇，收集接受替比夫定治疗前及分娩前血清标本；4例对照组孕妇(发生宫内感染及未发生宫内感染各2例)，收集分娩前血清标本；蛋白质芯片测定已筛选的30个细胞因子及趋化因子的浓度。②酶联免疫吸附试验(enzyme-linked immune sorbent assay，ELISA)：54例替比夫定组孕妇，其中免疫活化18例、免疫耐受36例，ELISA方法分别检测替比夫定治疗前和分娩前血清IL-2、IFN-γ、IL-4及IL-6浓度。统计学SPSS(PASW)18.0处理数据。结果： 1.替比夫定组母亲替比夫定治疗后较治疗前，血清IP-10浓度明显升高(P=0.049)。 2.发生宫内感染的母亲分娩前血清CCL20、IL-1β、IL-6、IFN-γ浓度高于未发生宫内感染的母亲。 3.免疫活化组和免疫耐受组孕妇经替比夫定治疗后，血清HBV DNA水平显著下降(P＜0.01)，但无病例出现HBeAg血清学转换。 4.无论是否存在免疫活化，与健康人群相比较，免疫活化组和免疫耐受组在治疗前和分娩前均表现为IL-2和IFN-γ高表达，而IL-4和IL-6低表达；两组治疗前IL-2、IFN-γ、IL-4和IL-6水平均无显著差异(P=0.604，0.332，0.097，0.714)；两组分娩前IL-2、IFN-γ、IL-4和IL-6水平亦无显著差异(P=0.611，0.839，0.553，0.833)。 5.免疫活化组分娩前较治疗前IL-4水平有升高(P=0.014)，但治疗前和分娩前其水平均在正常检测范围内，这种差异实际并无临床意义，而IL-2、IFN-γ和IL-6水平无显著变化(P=0.182，0.259，0.710)；免疫耐受组分娩前较治疗前IL-2、IFN-γ、IL-4和IL-6水平亦无显著变化(P=0.651，0.839，0.650，0.542)。结论： 1.慢性HBV感染孕妇经替比夫定治疗后IP-10的表达可能会增加。 2.慢性HBV感染孕妇分娩前血清CCL20、IL-1β和IFN-γ水平高表达可能与宫内感染发生有关。 3.慢性HBV感染孕妇妊娠中晚期血清Th1型细胞因子水平呈高表达、Th2型细胞因子水平呈低表达。 4.替比夫定短期治疗对孕妇Th1/Th2平衡影响较小，其参与阻断HBV母婴传播可能通过其他途径发挥作用。
[Abstract]:Objective:
The aim of this study was to investigate the immune status of pregnant women with HBV infection by measuring the levels of serum cytokines/chemokines related to HBV infection in pregnant women with different phenotypes of chronic hepatitis B virus (HBV), and to evaluate the effect of telbivudine treatment on pregnant women's immunity, so as to further explore the effect of telbivudine treatment on blocking mother-to-child transmission. Mechanism.
Method:
Serum samples of pregnant women with chronic hepatitis B surface antigen (HbsAg) and hepatitis B e antigen (HbeAg) positive and HBV DNA (>106 IU/ml) were collected from January 2012 to December 2013. Telbivudine was administered at 28 to 32 weeks of gestation in the Telbivudine group and untreated during pregnancy in the control group. To test methods are: (1) Protein chip test: 3 cases of pregnant women received tibivudine before and before delivery serum samples; 4 cases of pregnant women in control group (2 cases of intrauterine infection and 2 cases of non-intrauterine infection), collected serum samples before delivery; protein chip assay has been screened for 30 cytokines and chemokines. (2) Enzyme-linked immune sorbent assay (ELISA): 54 pregnant women in the tibivudine group, including 18 cases of immune activation, 36 cases of immune tolerance. Serum levels of IL-2, IFN-gamma, IL-4 and IL-6 were detected by ELISA before and before tibivudine treatment. Statistical SPSS (PASW) 18.0 was used to process the data.
Result:
1. telbivudine group had higher serum IP-10 concentration than telbivudine treatment before treatment (P=0.049).
2. The serum levels of CCL20, IL-1beta, IL-6 and IFN-gamma of the mothers with intrauterine infection before delivery were higher than those of the mothers without intrauterine infection.
3. The serum HBV DNA level of pregnant women in the immune activation group and the immune tolerance group decreased significantly after tibivudine treatment (P<0.01), but there was no serological change of HBeAg.
4. Compared with the healthy group, the levels of IL-2, IFN-gamma, IL-4 and IL-6 in the immune-activated group and the immune-tolerant group were significantly higher before and before delivery, but the levels of IL-2, IFN-gamma, IL-4 and IL-6 were not significantly different between the two groups (P=0.604, 0.332, 0.097, 0.714). There was no significant difference in IL-6 level between the two groups (P=0.611,0.839,0.553,0.833).
5. The levels of IL-4 in the immune-activated group were higher than those before delivery (P=0.014), but the levels of IL-2, IFN-gamma and IL-6 in the immune-tolerant group were all within the normal range before and before delivery. There was no significant difference in the levels of IL-2, IFN-gamma and IL-6 (P=0.182, 0.259, 0.710), and the levels of IL-2, IFN-gamma, IL-4 and IL-6 in the immune-tolerant group were also higher than those before delivery (P=0.182, 0.259, There was no significant change (P=0.651,0.839,0.650,0.542).
Conclusion:
1. the expression of IP-10 may increase in pregnant women with chronic HBV infection after telbivudine treatment.
2. The high levels of serum CCL20, IL-1beta and IFN-gamma in pregnant women with chronic HBV infection before delivery may be related to the occurrence of intrauterine infection.
3. The levels of serum Th1 cytokines in pregnant women with chronic HBV infection in the middle and late stages of pregnancy were high, but the levels of Th2 cytokines were low.
4. Telbivudine has little effect on Th1/Th2 balance in pregnant women, and its involvement in blocking mother-to-child transmission of HBV may play a role in other ways.
【学位授予单位】：蚌埠医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R714.251

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