人源可溶性B淋巴细胞刺激因子（hsBAFF）对小鼠特异性免疫细胞的免疫调节作用及其机理研究

发布时间：2018-10-08 08:36

【摘要】：本文运用细胞培养、流式细胞分析、激光共聚焦显微镜分析等免疫学和细胞学技术，综合研究和观察了hsBAFF对小鼠B淋巴细胞的免疫功能活性及其胞内Ca~(2+)信号变化，T淋巴细胞亚群分布和NK细胞活性影响，探讨了hsBAFF对机体特异性免疫细胞乃至整体免疫系统的调控作用及其作用机制。结果如下： 1 hsBAFF注射小鼠体重和血液18项常规指标变化选用48只健康ICR小鼠，雌雄各半，随机分为对照组和5个不同剂量的hsBAFF处理组，处理组分别每日腹腔注射含hsBAFF 0.01、0.1、0.5、1、2mg／kg体重的PBS溶液，对照组注射同等剂量的PBS溶液。每天对各组小鼠称重，分别在第4、8天测定小鼠血液18项常规指标。结果表明：在整个实验期间，小鼠体重均随日龄而增加，各组间无显著差异；各组血液18项常规指标没有显著变化，只在第4天时个别指标有波动，但均在生理正常允许范围内。提示：hsBAFF对小鼠的正常生理指标无明显影响，表明其对机体没有明显的毒害作用，为hsBAFF进入临床阶段的研究提供了毒理学证据。 2 hsBAFF注射小鼠脾脏B淋巴细胞活性和血浆IgM、IgA、IgG含量变化研究选用40只健康ICR小鼠，雌雄各半，随机分成1个对照组和3个不同剂量的hsBAFF处理组，每组10只。处理组每日腹腔注射含hsBAFF 0.1、0.5和1mg／kg体重的PBS溶液，对照组注射同等剂量的PBS溶液。分别在第4、8天检测脾脏B淋巴细胞的增殖活性和对LPS免疫反应以及血清IgM、IgA、IgG的含量变化。结果表明：hsBAFF注射组小鼠脾脏B淋巴细胞的自然增殖活性显著升高并呈剂量效应关系，在实验第8天B淋巴细胞对LPS的刺激增殖活性明显上升；注射第4、8天时，hsBAFF注射组小鼠血清IgM含量升高近两倍，IgA含量也有显著升高。血清IgG含量在实验第4天与对照组相当，但第8天时0.5-1.0mg／kghsBAFF注射组明显高于对照组。提示：hsBAFF可以通过提高B淋巴细胞的增殖活性和免疫反应及增加血清IgM，IgA和IgG的含量增强机体的免疫反应。 3 hsBAFF注射对小鼠脾脏CD4~+和CD8~+ T淋巴细胞及NK细胞活性调节作用研究选用40只健康ICR小鼠，雌雄各半，随机分成1个对照组和4个hsBAFF处理组，每组8只。HsBAFF处理组分别每日腹腔注射hsBAFF(0.01、0.1、0.5和2mg／kg体重)的PBS溶液，对照组注射同等剂量的PBS溶液。实验第8天
[Abstract]:In this paper, immunological and cytological techniques such as cell culture, flow cytometry and laser confocal microscopy were used. The effects of hsBAFF on the immune function of mouse B lymphocytes and the changes of Ca~ _ (2) signal were studied. The distribution of T lymphocyte subsets and the activity of NK cells were observed. The regulation and mechanism of hsBAFF on specific immune cells and whole immune system were studied. The results are as follows: 1 the changes of body weight and 18 routine indexes in blood of hsBAFF injected mice 48 healthy ICR mice were selected. Both sexes were randomly divided into two groups: control group (n = 5) and hsBAFF treatment group (n = 5). The treated group was intraperitoneally injected with PBS solution containing hsBAFF 0.01g / kg 0.5g / kg, and the control group was given PBS solution of the same dose. Each group of mice were weighed every day and 18 routine indexes of blood were measured on the 4th day. The results showed that during the whole experiment, the body weight of the mice increased with the age of the day, and there was no significant difference among the groups, and there was no significant change in the 18 routine indexes in the blood of each group, but only the individual indexes fluctuated on the 4th day. But it is within the range of physiological normal. The results suggested that there was no obvious effect on the normal physiological indexes of mice, which indicated that the BAFF had no obvious toxic effect on the body, which provided toxicological evidence for the study of hsBAFF entering the clinical stage. 2 the changes of splenic B lymphocyte activity and plasma IgM,IgA,IgG content in hsBAFF injected mice were studied in 40 healthy ICR mice, half male and half male. They were randomly divided into one control group and three different doses of hsBAFF treatment group with 10 rats in each group. The treatment group was intraperitoneally injected with PBS solution containing hsBAFF 0.1g 0.5 and 1mg/kg body weight daily, while the control group was injected with the same dose of PBS solution. The proliferative activity of splenic B lymphocytes, the immune response to LPS and the content of serum IgM,IgA,IgG were detected on the 4th day. The results showed that the natural proliferative activity of B lymphocytes in the spleen of mice injected with 1% hsBAFF was significantly increased in a dose-dependent manner. On the 8th day of the experiment, the proliferative activity of B lymphocytes stimulated by LPS was obviously increased. The level of serum IgM in hsBAFF injection group was increased by nearly twice as much as that of the control group on the 8th day after injection of hsBAFF. The level of serum IgG was similar to that of the control group on the 4th day, but on the 8th day, the level of 0.5-1.0mg/kghsBAFF injection group was significantly higher than that of the control group. These results suggest that IgM,IgA and IgG can enhance the immune response by increasing the proliferative activity and immune response of B lymphocytes and the contents of serum IgM,IgA and IgG. 3The effect of hsBAFF injection on the activity regulation of CD4~ and CD8~ T lymphocytes and NK cells in spleen of mice was studied in 40 healthy ICR mice, half male and half male. The rats were randomly divided into control group and 4 hsBAFF treatment groups. 8 rats in each group were intraperitoneally injected with PBS solution of hsBAFF (0.01g 0.1g / kg) and 2mg/kg body weight, respectively. The control group was injected with the same dose of PBS solution. The 8th day of the experiment
【学位授予单位】：南京师范大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R392

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