【作者】 李红；

【导师】 韩德五；

【作者基本信息】 山西医科大学 ， 生理学， 2006， 博士

【摘要】 目前,越来越多的资料揭示了宿主免疫系统在慢性乙型肝炎病毒(Hepatic B virus,HBV)感染中的重要作用。疾病发展和转归的主要因素在于宿主的免疫功能,肠源性内毒素血症(intestinal endotoxemia,IETM)为其主要的影响因素之一。我所诸多动物实验和临床研究发现,急慢性肝炎、肝硬化动物和患者所伴之IETM与肝脏免疫功能密切相关。然而,具体机制仍有待进一步研究。本论文共分三个部分。第一部分:IETM阳性与阴性对慢性肝炎患者免疫功能的影响;第二部分:IETM相伴之高组胺血症的发生机制及其对免疫功能的影响;第三部分:IETM对细胞免疫功能的影响。第一部分:探讨IETM阳性与阴性对慢性肝炎患者免疫功能的影响。实验一、二:选取慢性乙肝患者80例,根据测定的血浆内毒素水平,将其分为内毒素(ET)阳性组和阴性组,分别检测血清白细胞介素10、12(IL-10、IL-12)、干扰素γ(IFN-γ)、白细胞介素4(IL-4)浓度。并结合乙型肝炎病毒e抗原(HBeAg)、乙肝病毒脱氧核糖核酸(HBVDNA)、血清谷丙转氨酶(ALT)以及总胆红素(TBIL)进行分析研究。结果显示,1.肝炎患者(total patients)的各项指标均有不同程度异常。在慢性肝炎患者中,内毒素血症的发生率为41/80(51.25%),内毒素阳性组(ET positive)与阴性组(ET negative)比较,ALT、TBIL、IL-4、IL-10水平均显著升高,而IL-12水平和Th1/Th2比值明显降低。2.HBeAg阳性组IL-4与IL-10水平明显高于阴性组,而IL-12和IFN-γ水平明显低于阴性组。HBVDNA阳性组ET、IL-4与IL-10水平明显高于阴性组,而IL-12水平明显低于阴性组,提示HBeAg阳性与HBVDNA阳性也与IETM有关。3.乙肝患者内毒素水平分别与IL-4、IL-10水平呈显著正相关,与IL-12水平呈明显负相关。在内毒素阳性组患者,内毒素水平分别与IL-4、IL-10水平呈显著正相关,与IL-12、Th1/Th2比值呈负相关,而在阴性组则无此相关性。结果提示:IETM是引起Th1/Th2比值下降的原因之一。IETM可以引起IL-12水平降低即Th1降低,IL-4、IL-10水平升高即Th2升高而导致Th1/Th2失衡,病毒难以清除导致乙肝慢性化。实验三:连续收集31例患者,根据临床分型:慢性丙型肝炎(chronic hepatitis C,CHC)15例,丙肝后肝硬化(HCV-related liver cirrhosis,CLC)10例,丙肝相关性肝癌(HCV-related hepatocellular carcinoma,HCC)6例,选取18例健康体检人群为正常对照,采血检测血浆内毒素(ET)、血清谷丙转氨酶(ALT)、总胆红素(TBIL)、血清白细胞介素10、12(IL-10、更多还原

【Abstract】 Now more and more documents have revealed immune system of hosts takes an important role on chronic HBV infection.The immune system of hosts are the major factor to influence the development and turnover of diseases.Moreover,intestinal endotoxemia(IETM)is one of the most important factors.We have discovered that intestinal endotoxemia in patients or animals with acute hepatitis、chronic hepatitis、liver cirrhosis is closely correlated with liver immune function. However, the concrete mechanism still to remain pending further investegation.This thesis is composed of three parts:Part 1:The effect of IETM positive and IETM negative on the immune functions of the chronic hepatitis patients;Part 2:The pathogenesis of histaminemia following IETM and its effect on immune functions;Part 3:The effect of IETM on cellular immune function.Part 1: To investigate the effect of IETM positive and IETM negative on the immune functions of the chronic hepatitis patient.Experiment one and two: peripheral blood were collected from patients with chronic hepatitis B(n=80) and healthy individuals(n=18).According to plasma endotoxin concentration,total patients were divided into two groups:ET positive and ET negative.Serum IL-10、IL-12、IFN-γ、and IL-4 concentration were detected. In addition,we studied serum HBeAg、HBVDNA、ALT and TBIL.The results showed :1.The observed indexes of total patients were all increased.The incidence of IETM is 41/80(51.25%)in chronic hepatitis patients.The levels of ALT、TBIL、IL-4、IL-10 in ET positive were significantly higher than in ET negative and the level of IL-12 and the ratio of Th1/Th2 was decreased obviously.2.The levels of IL-4 and IL-10 were significantly higher in HBeAg positive than in HBeAg negative while the levels of IL-12 and IFN-γwere lower than in HBeAg negative.The levels of ET、IL-4 and IL-10 in HBVDNA positive were higher than in HBVDNA negative while the level of IL-12 was obviously lower than in HBVDNA negative.This results suggest that HBeAg positive and HBVDNA positive were also correlated with IETM.3.The level of endotoxin were positively correlated with IL-4、IL-10 and negatively correlated with IL-12 in total hepatitis. The level of endotoxin in ET positive were positively correlated with IL-4、IL-10 while it were negatively correlated with IL-12 and Th1/Th2 ratio and there was no correlation in ET negative.The results suggested:IETM is one of reason to cause low level Th1/Th2 ratio.IETM may更多还原