【摘要】：目的： 本研究擬通過測定不同表型慢性乙型肝炎病毒(hepatitis B virus，HBV)感染孕婦HBV相關(guān)血清細胞因子/趨化因子水平，，了解HBV感染孕婦的免疫狀態(tài)；評估替比夫定治療對孕婦免疫的影響，進一步從免疫層面探討替比夫定治療阻斷母嬰傳播的機制。 方法： 收集2012年1月至2013年12月檢測乙型肝炎表面抗原(hepatitis B surfaceantigen，HbsAg)及乙型肝炎e抗原(hepatitis B e antigen，HbeAg)均為陽性且HBVDNA≥106IU/mL的慢性HBV感染孕婦血清標本，替比夫定組孕28~32周開始服用替比夫定，對照組孕期未予治療。主要試驗方法有：①蛋白質(zhì)芯片試驗：3例替比夫定組孕婦，收集接受替比夫定治療前及分娩前血清標本；4例對照組孕婦(發(fā)生宮內(nèi)感染及未發(fā)生宮內(nèi)感染各2例)，收集分娩前血清標本；蛋白質(zhì)芯片測定已篩選的30個細胞因子及趨化因子的濃度。②酶聯(lián)免疫吸附試驗(enzyme-linked immune sorbent assay，ELISA)：54例替比夫定組孕婦，其中免疫活化18例、免疫耐受36例，ELISA方法分別檢測替比夫定治療前和分娩前血清IL-2、IFN-γ、IL-4及IL-6濃度。統(tǒng)計學(xué)SPSS(PASW)18.0處理數(shù)據(jù)。 結(jié)果： 1.替比夫定組母親替比夫定治療后較治療前，血清IP-10濃度明顯升高(P=0.049)。 2.發(fā)生宮內(nèi)感染的母親分娩前血清CCL20、IL-1β、IL-6、IFN-γ濃度高于未發(fā)生宮內(nèi)感染的母親。 3.免疫活化組和免疫耐受組孕婦經(jīng)替比夫定治療后，血清HBV DNA水平顯著下降(P＜0.01)，但無病例出現(xiàn)HBeAg血清學(xué)轉(zhuǎn)換。 4.無論是否存在免疫活化，與健康人群相比較，免疫活化組和免疫耐受組在治療前和分娩前均表現(xiàn)為IL-2和IFN-γ高表達，而IL-4和IL-6低表達；兩組治療前IL-2、IFN-γ、IL-4和IL-6水平均無顯著差異(P=0.604，0.332，0.097，0.714)；兩組分娩前IL-2、IFN-γ、IL-4和IL-6水平亦無顯著差異(P=0.611，0.839，0.553，0.833)。 5.免疫活化組分娩前較治療前IL-4水平有升高(P=0.014)，但治療前和分娩前其水平均在正常檢測范圍內(nèi)，這種差異實際并無臨床意義，而IL-2、IFN-γ和IL-6水平無顯著變化(P=0.182，0.259，0.710)；免疫耐受組分娩前較治療前IL-2、IFN-γ、IL-4和IL-6水平亦無顯著變化(P=0.651，0.839，0.650，0.542)。 結(jié)論： 1.慢性HBV感染孕婦經(jīng)替比夫定治療后IP-10的表達可能會增加。 2.慢性HBV感染孕婦分娩前血清CCL20、IL-1β和IFN-γ水平高表達可能與宮內(nèi)感染發(fā)生有關(guān)。 3.慢性HBV感染孕婦妊娠中晚期血清Th1型細胞因子水平呈高表達、Th2型細胞因子水平呈低表達。 4.替比夫定短期治療對孕婦Th1/Th2平衡影響較小，其參與阻斷HBV母嬰傳播可能通過其他途徑發(fā)揮作用。
[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.
【學(xué)位授予單位】：蚌埠醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R714.251

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