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目的:观察C57BL/6N-Tg(1.28HBV)/Vst乙型肝炎病毒(HBV)转基因小鼠复合四氯化碳(CCln 4)腹腔注射诱导乙型肝炎背景下肝纤维化模型小鼠肝内淋巴细胞亚群变化特点,并分析其与血清HBV DNA及肝组织羟脯氨酸(Hyp)含量的相关性。n 方法:HBV-Tg小鼠予10% CCln 4腹腔注射诱导加速肝纤维化形成,以血清HBV DNA、HBsAg、HBeAg水平和肝组织HBsAg表达情况评价模型小鼠病毒学特征,肝组织HE、天狼猩红染色及肝组织Hyp含量检测小鼠肝脏炎症及纤维化程度,流式细胞术观察肝内T淋巴细胞、B淋巴细胞、CD4n +T淋巴细胞、CD8n +T淋巴细胞、自然杀伤(NK)细胞、自然杀伤T淋巴(NKT)细胞分布情况。组间数据比较采用单因素方差分析,LSD进行两两比较;Pearson相关性分析上述各淋巴细胞亚群与血清HBV DNA、肝组织Hyp含量的相关性。n 结果:HBV-Tg复合CCln 4模型组小鼠血清HBsAg、HBeAg及肝组织HBsAg均呈阳性表达,血清HBV DNA载量> 1×10n 6 IU/ml。与野生型对照组相比,复合模型组小鼠肝组织Hyp含量显著升高[(196.39±38.14)μg/g与(347.67±59.53)μg/g,n P < 0.01],肝组织炎症及纤维化程度加重,肝内CD4 n +T、NK、NKT细胞占淋巴细胞比例均显著减少(n P < 0.01),而CD8 n +T淋巴细胞(30.58%±2.89%与46.50%±2.24%,n P < 0.01)和B淋巴细胞(28.82%±2.24%与37.10%±8.59%, n P < 0.05)比例明显增多。血清HBV DNA水平与肝内T淋巴细胞比例呈正相关( n r = 0.413,n P < 0.05),与NK细胞比例呈负相关( n r = -0.419,n P < 0.05);肝组织Hyp含量与CD4 n +T淋巴细胞(n r = -0.871)、NK细胞(n r = -0.716)、NKT细胞(n r = -0.876)比例均呈负相关(n P值均< 0.01),与CD8n +T淋巴细胞(n r = 0.852)、B淋巴细胞(n r = 0.593)比例均呈正相关(n P值均 1 × 10 n 6 IU / ml. Compared with the wild-type control group, liver tissue Hyp content of the composite model group was significantly higher [(196.39 ± 38.14) μg /g and (347.67 ± 59.53) μ g/g, n P < 0.01). The degree of inflammation and fibrosis in liver tissues was aggravated, and the proportion of all intrahepatic CD4+T, NK and NKT cells was significantly reduced ( n P < 0.01), while the proportion of CD8+T lymphocytes (30.58% ± 2.89% vs. 46.50% ± 2.24%, n P < 0.01) and B lymphocytes (28.82% ± 2.24% vs. 37.10% ± 8.59%, n P < 0.05) was significantly increased. Serum HBV DNA level was positively correlated with the proportion of intrahepatic T lymphocytes ( n r = 0.413, n P < 0.05), and negatively correlated with the proportion of NK cells ( n r = -0.419, n P < 0.05). Liver tissue Hyp content was negatively correlated with the proportion of all CD4+T lymphocytes ( n r = -0.871), NK cells (n r = -0.716), and NKT cells (n r = -0.876) (all n P < 0.01), and positively correlated with the proportion of all CD8 + T lymphocytes ( n r = 0.852), and B lymphocytes (n r = 0.593) (all n P < 0.01).n Conclusion:HBV-Tg composite CCl4 mice model can induce positive HBV virological indicators, liver inflammation and fibrosis in mice model of hepatitis B coexisting with fibrosis. This model has the features of immune disorder of liver lymphocyte similar to human disease, and the immune disorder of intrahepatic lymphocytes is correlated with HBV viral load and liver fibrosis degree.