本文選題：白細(xì)胞介素-8　切入點(diǎn)：乙型肝炎病毒　出處：《安徽醫(yī)科大學(xué)》2017年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：目的探討白細(xì)胞介素8(Interleukin,IL-8)在乙型肝炎相關(guān)性慢加急性肝功能衰竭(HBV-acute-on-chronic liver failure,HBV-ACLF)患者中的水平變化及臨床價(jià)值。方法對(duì)62例HBV-ACLF患者和57例HBV患者采用免疫組化技術(shù)分析肝組織IL-8水平與分布情況,利用ELISA技術(shù)測(cè)定血清IL-8水平。同時(shí)測(cè)定HBV-DNA和肝功能指標(biāo),如血清丙氨酸氨基轉(zhuǎn)移酶(Alanine aminotransferase,ALT)、堿性磷酸酶(Alkaline phosphatase,ALP)、天門(mén)冬氨酸氨基轉(zhuǎn)移酶(Aspartate transaminase,AST)、總膽紅素和肌酐等。按照HBV-ACLF組患者的臨床轉(zhuǎn)歸情況,將HBV-ACLF組分為好轉(zhuǎn)組和死亡組,計(jì)算MELD評(píng)分。以Ficoll密度梯度離心法分離HBV-ACLF患者外周血中外周血單個(gè)核細(xì)胞(Peripheral blood mononuclear cells,PBMCs)并分為四組,分別為空白對(duì)照、IL-8組、α-干擾素(Alpha-interferon,IFN-α)組和IL-8+IFN-α聯(lián)合處理組。經(jīng)過(guò)6h處理作用后,收集細(xì)胞蛋白,通過(guò)RT-q PCR、Western Blot技術(shù)檢測(cè)JAK-STAT信號(hào)途徑中主要分子及蛋白的表達(dá)。結(jié)果肝組織或外周血中,HBV-ACLF患者的IL-8含量高于HBV患者,同時(shí)顯著高于對(duì)照組;且經(jīng)Pearson相關(guān)性分析,HBV500 IU/ml時(shí)血清IL-8與HBV-DNA水平呈正相關(guān)(r=0.416,P0.05)。與HBV患者和對(duì)照組相比,HBV-ACLF患者血清中ALT,AST,ALP,總膽紅素和肌酐含量均有明顯增加。血清中IL-8含量與ALT和AST有顯著的正相關(guān)性(r=0.216,P0.05;r=0.317,P0.05)。按照HBV-ACLF組患者的臨床轉(zhuǎn)歸情況,將HBV-ACLF組分為好轉(zhuǎn)組和死亡組,死亡組患者的IL-8含量顯著高于好轉(zhuǎn)組,差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。且HBV-ACLF患者的血清IL-8含量與MELD評(píng)分呈顯著正相關(guān)(r=0.313,P0.05)。四組HBV-ACLF患者的PBMCs中IFN-α處理組STAT1、STAT2、IRF9等相關(guān)信號(hào)轉(zhuǎn)導(dǎo)分子及抗病毒蛋白Mx A的表達(dá)最高(P0.05),IL-8與IFN-α聯(lián)合處理組的信號(hào)分子及蛋白表達(dá)最低(P0.05)。與空白對(duì)照組相比,IL-8處理組表達(dá)水平顯著降低(P0.05),提示IL-8可能通過(guò)某些機(jī)制影響JAK-STAT信號(hào)轉(zhuǎn)導(dǎo)通路,從而對(duì)抗病毒。蛋白的表達(dá)有一定的抑制作用。IL-8與IFN-α聯(lián)合處理組的信號(hào)分子及蛋白表達(dá)明顯低于IFN-α處理組(P0.05),說(shuō)明當(dāng)IL-8存在時(shí),IFN-α的抗病毒表達(dá)明顯受到了抑制,從而提示IL-8可能對(duì)IFN-α的抗病毒效應(yīng)有一定的負(fù)向調(diào)節(jié)作用。結(jié)論HBV-ACLF患者的肝組織及血清IL-8水平與慢性乙肝患者組和健康對(duì)照組相比,均有明顯的升高,且血清IL-8水平與其肝臟炎癥損傷程度具有相關(guān)性。IL-8對(duì)HBV-ACLF患者的外周血單個(gè)核細(xì)胞內(nèi)JAK-STAT途徑分子和Mx A等抗病毒蛋白的表達(dá)有一定的抑制作用,并對(duì)IFN-α的抗病毒效應(yīng)具有一定的負(fù)向調(diào)節(jié)作用。
[Abstract]:Objective to investigate the level and clinical value of interleukin 8 (IL-8) in patients with chronic hepatitis B associated with chronic liver failure and acute hepatic failure. Methods 62 patients with HBV-ACLF and 57 patients with HBV were analyzed by immunohistochemical technique. The level and distribution of weaving IL-8, Serum IL-8, HBV-DNA and liver function were measured by ELISA technique. For example, serum alanine aminotransferase, alkaline phosphatase, aspartate transaminase, total bilirubin and creatinine. According to the clinical outcome of patients with HBV-ACLF, the HBV-ACLF group was divided into improvement group and death group. MELD score was calculated. Peripheral blood mononuclear cells were isolated from peripheral blood of patients with HBV-ACLF by Ficoll density gradient centrifugation. They were divided into four groups: blank control group (IL-8), 偽 -interferon Alpha-interferon IFN- 偽 (IFN- 偽) group and IL-8 IFN- 偽 combined treatment group. The expression of major molecules and proteins in JAK-STAT signaling pathway was detected by RT-q PCR Western Blot. Results the IL-8 content of HBV-ACLF patients in liver tissue or peripheral blood was higher than that in HBV patients and significantly higher than that in control group. After Pearson correlation analysis, the serum IL-8 and HBV-DNA levels were positively correlated with those of HBV patients and controls. Compared with HBV patients and control group, serum alt, total bilirubin and creatinine levels in HBV-ACLF patients were significantly increased, and IL-8 levels were significantly higher than those in ALT and AST patients. There was a positive correlation between 0.216m and 0.216p 0.05. According to the clinical outcome of patients in HBV-ACLF group, The HBV-ACLF group was divided into improved group and death group. The IL-8 content in the dead group was significantly higher than that in the improved group. The difference was statistically significant (P 0.05). There was a significant positive correlation between serum IL-8 content and MELD score in patients with HBV-ACLF. The highest expression of IL-8 and IFN- 偽 related signal transduction molecules, such as STAT1, STAT2, IRF9, and anti-virus protein MxA, were observed in PBMCs of four groups of HBV-ACLF patients. Compared with the control group, the level of signal molecule and protein expression in the combined treatment group was significantly lower than that in the control group, suggesting that IL-8 might affect the JAK-STAT signal transduction pathway through some mechanisms. The expression of signal molecules and proteins in IL-8 and IFN- 偽 treated group was significantly lower than that in IFN- 偽 treatment group (P 0.05), which indicated that the antiviral expression of IFN- 偽 was significantly inhibited when IL-8 was present. Conclusion the level of IL-8 in liver and serum of HBV-ACLF patients is significantly higher than that of chronic hepatitis B patients and healthy controls. The level of serum IL-8 was correlated with the degree of liver inflammation. IL-8 could inhibit the expression of JAK-STAT pathway molecules and MxA antiviral proteins in peripheral blood mononuclear cells (PBMC) of HBV-ACLF patients. And the antiviral effect of IFN- 偽 was negatively regulated.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R512.62;R575.3

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