胸腺肽联合ADV治疗LAM耐药慢乙肝患者前后IL-10和IL-18水平变化及意义

发布时间：2018-05-14 12:28

本文选题：骨桥蛋白 + 抗体　；参考：《石河子大学》2013年硕士论文

【摘要】：目的：建立沙鼠肝泡状棘球蚴动物模型，外源性给予抗OPN抗体，根据在不同生长阶段，沙鼠肝泡球蚴及转移组织中IL-2、IL-5、IL-10及TNF-α因子的表达水平，来探讨这四种因子在沙鼠肝泡状棘球蚴侵袭性生长和转移中的作用，观察抗OPN抗体对泡状棘球蚴生长发育的影响。方法：选择4-6周龄健康长爪沙鼠120只，雌性，体重（30±5）g。随机分为三组，采用开腹直视下肝脏穿刺接种多房棘球蚴原头节混悬液的方法(0.15ml/只)，建立肝泡状棘球蚴动物模型。一组单纯接种泡状棘球蚴组（模型组），二组在接种泡状棘球蚴同时予以抗OPN抗体干预（实验组），三组在接种泡状棘球蚴同时予以兔血清干预（对照组）。分别将三组接种泡状棘球蚴的沙鼠随机分成6小组，每小组10只，分别为感染140天、180天、220天、260天组。于相应时间处死各组沙鼠，观察泡状棘球蚴的生长、转移等情况；免疫组化法测定肝泡状棘球蚴及转移组织标本中的IL-2，IL-5，IL-10及TNF-α因子的表达。结果： 1.140天、180天、220天组时实验组与对照组、实验组与模型组囊湿重有显著性差异（F值分别为8.647，36.96，9.12，p值均小于0.05），，而对照组与模型之间比较无差异（P㧐0.05）。 2.观察泡状棘球蚴转移现象，发现肺转移灶较少见，而胸廓淋巴结转移率较高，未见脑转移灶。统计结果显示：140天、180天、组时实验组与对照组、实验组与模型组胸廓淋巴结转移率有显著性差异（P㩳0.05），220天组时实验组与对照组，实验组与模型组胸廓淋巴结转移率无显著性差异（P㧐0.05）。 3. HE染色结果显示:在140天、180天、220天时间段，实验组与对照组、实验组与模型组间E.m囊壁病理的改变无显著性差异（P㧐0.05）。 4.免疫组化染色结果显示：肝泡型棘球蚴组织中可见IL-2，IL-5， IL-10及TNF-α因子不同程度的表达，定位于细胞浆，主要分布在肝泡状棘球蚴纤维囊壁的生发层，细胞浆中可见黄色、棕黄色或棕褐色等阳性颗粒；140天、180天组时IL-5，IL-10的表达在实验组与对照组、实验组与模型组比较有显著性差异（P㩳0.05）；140天、180天组时时间段，实验组与对照组、实验组与模型组IL-2及TNF-α的阳性细胞率比较无显著性差异（P㧐0.05），220天时时间段，实验组与对照组、实验组与模型组IL-2，IL-5，IL-10及TNF-α的阳性细胞率比较无显著性差异。结论：IL-2，IL-5，IL-10及TNF-α共同参与了宿主与肝泡状棘球蚴相互间中晚期免疫进程。外源性给予抗OPN抗体可使肝泡状棘球蚴组织中IL-5，IL-10的表达减低，这可能是抑制肝泡状棘球蚴中晚期侵袭性生长和转移的机制之一。
[Abstract]:Objective: to establish an animal model of hepatic alveolar echinococcosis in gerbils, and give exogenous anti OPN antibody. According to the expression levels of IL-2, IL-5, IL-10 and TNF- 伪 in liver alveolar hydatid and metastatic tissues of gerbils at different growth stages. To investigate the role of these four factors in the invasive growth and metastasis of hydatid alveolar hydatid in gerbils, and to observe the effect of anti OPN antibody on the growth and development of hydatid alveolar hydatid. Methods: 120 healthy gerbils aged 4-6 weeks, female, weight 30 卤5g. Three groups were randomly divided into three groups. The hepatic alveolar hydatid model was established by liver puncture and inoculation of multilocularis echinococci with the suspension of the original head ganglion of Echinococcus multilocularis (Echinococcus multilocularis). One group was inoculated with alveolar echinococcus (model group), the other group was inoculated with OPN antibody (experimental group) and three groups were inoculated with rabbit serum (control group). Three groups of gerbils inoculated with hydatid alveolar echinococci were randomly divided into 6 groups with 10 rats in each group. The growth and metastasis of hydatid alveolar echinococci were observed and the expression of IL-2IL-5 IL-10 and TNF- 伪 in liver alveolar echinococci and metastatic tissues were detected by immunohistochemical method. Results: There was significant difference between the experimental group and the control group in the wet weight of the capsule between the experimental group and the control group at day 1.140 and day 180 and 220d, respectively. The F value of the experimental group and the model group was 8.647 / 36.96 / 9.12p < 0.05 respectively, but there was no significant difference between the control group and the model group (P < 0.05). 2. The phenomenon of alveolar echinococcosis metastasis was observed. The pulmonary metastasis was rare, but the thoracic lymph node metastasis rate was higher, and no brain metastasis was found. The statistical results showed that there were significant differences between the experimental group and the control group at 140 days to 180 days, and the rates of thoracic lymph node metastasis between the experimental group and the model group at 220 days. There was no significant difference between the experimental group and the model group in the rate of thoracic lymph node metastasis. 3. The results of HE staining showed that there was no significant difference between the experimental group and the control group and between the experimental group and the model group in the pathological changes of the E m cyst wall at the time of 140 days, 180 days and 220 days, and there was no significant difference between the experimental group and the control group. 4. Immunohistochemical staining showed that IL-2IL-5, IL-10 and TNF- 伪 were expressed in different degrees in the liver alveolar hydatid tissues, located in the cytoplasm, mainly distributed in the germinal layer of the fibrous wall of the hepatic alveolar echinococcus, and yellow in the cytoplasm. The expression of IL-5 IL-10 in the experimental group and the control group was significantly different from that in the experimental group and the model group at the time of 140 days and 180 days respectively, and the experimental group and the control group had a significant difference in the expression of IL-5 and IL-10 during the period of 140 days and 180 days, respectively, between the experimental group and the model group, and between the experimental group and the control group. There was no significant difference in the positive cell rates of IL-2 and TNF- 伪 between the experimental group and the model group. There was no significant difference between the experimental group and the control group, between the experimental group and the model group in the positive cell rate of IL-10 and TNF- 伪. Conclusion IL-10 and TNF- 伪 play an important role in the immune process between the host and the liver alveolar hydatid. Exogenous anti OPN antibody can reduce the expression of IL-5 and IL-10 in liver alveolar hydatid tissues, which may be one of the mechanisms of inhibiting the invasive growth and metastasis of hepatic alveolar echinococci.
【学位授予单位】：石河子大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R512.62

【参考文献】

中国期刊全文数据库前10条

1 ;病毒性肝炎防治方案[J];传染病信息;2000年04期

2 张宜俊;;慢性乙型肝炎免疫治疗若干问题[J];传染病信息;2005年03期

3 杨丽;帅萍;;拉米夫定耐药机制及对策[J];赣南医学院学报;2010年02期

4 邹晓毅,姚云清;机体清除乙型肝炎病毒免疫机制研究新进展[J];国外医学.病毒学分册;2005年02期

5 陈开森;IL-18生物学作用研究进展[J];九江学院学报(自然科学版);2004年04期

6 纪翠霞;胡九东;邢练军;季光;王磊;;乙型肝炎慢性化机制的研究现状[J];临床肝胆病杂志;2012年02期

7 贺荣;李国坚;吴继周;吴健林;罗双艳;黄爱春;李兰兰;宁秋悦;;HBV感染相关性慢性肝病IL-18的表达及临床意义研究[J];现代免疫学;2011年02期

8 高德民;王凤山;;胸腺肽α1的特征与功能综述[J];中国生化药物杂志;2007年02期

9 佟春玲;陆涛峰;余露露;章嘎;巴音吉日嘎拉;关伟军;马月辉;;IL-18在临床疾病中的作用[J];生物技术通报;2009年S1期

10 邓俊;张欣欣;;核苷(酸)类药物耐药机制及其对策[J];中国实用内科杂志;2007年17期