垂体促肾上腺皮质激素腺瘤与免疫系统功能关系的研究

发布时间：2018-06-10 18:00

本文选题：垂体ACTH腺瘤 + 淋巴细胞亚群　；参考：《北京协和医学院》2016年博士论文

【摘要】：研究背景：垂体腺瘤是颅内常见肿瘤,发病率约居于原发颅内肿瘤的第三位。20岁之后,垂体腺瘤是鞍区占位病变最常见的病因,在所有颅内肿瘤中所占比例高达10%。[1]库欣病又称垂体促肾上腺皮质激素依赖性库欣综合征,绝大多由垂体促肾上腺皮质激素依赖性腺瘤(垂体ACTH腺瘤)引起,发病率约占全部原发垂体腺瘤的13.1%。[2]虽然ACTH腺瘤绝大多数为良性肿瘤,但临床上垂体ACTH腺瘤患者经常容易并发各种感染。[3]基于神经-内分泌-免疫网络学说,垂体处于NEI网络的中心,ACTH腺瘤所促进分泌的皮质醇也已经被证实能够广泛而深刻影响免疫系统,因此垂体ACTH腺瘤患者的免疫系统受到肿瘤因素、神经系统和内分泌系统的多重复杂影响。通过研究ACTH腺瘤患者的免疫功能能够有助于探讨ACTH腺瘤的发生、发展机制,并能够指导临床围手术期患者管理,减少感染尤其是重症感染的发生率。研究目的：综合分析垂体ACTH腺瘤患者的免疫功能；探讨垂体ACTH腺瘤发生、发展、复发的潜在免疫学机制；探究手术对垂体ACTH腺瘤患者免疫功能的影响；指导临床围手术期管理,减少感染发生率。研究方法：采集患者外周血液学标本免疫学方面：通过流式细胞仪检测入组患者术前、术后淋巴细胞亚群11项水平；检测免疫球蛋白3项(IgG、IgA、IgM)以评估体液免疫,同时通过检测患者补体2项(C3/C4),白介素6、白介素10作为完整评估免疫系统功能的补充。内分泌学方面：检测垂体ACTH腺瘤患者术前后血总皮质醇、24小时尿游离皮质醇、ACTH水平。1. 检测和统计垂体ACTH腺瘤患者术前的免疫指标,了解垂体ACTH腺瘤患者的免疫功能状况和特点；2. 通过检测和对比垂体ACTH腺瘤患者与垂体无功能腺瘤患者的术前免疫学指标,探究垂体ACTH腺瘤在垂体腺瘤中免疫功能上的特性；3. 通过分别检测和统计实验组(垂体ACTH腺瘤患者)及对照组(垂体无功能腺瘤患者)手术前后免疫学指标的变化,探究手术对垂体ACTH腺瘤患者免疫功能的影响；4. 通过对应的垂体ACTH腺瘤患者免疫指标与内分泌指标,探究二者之间的联系和影响；5. 整理和统计垂体ACTH腺瘤患者在围手术期感染的情况以寻求从免疫学上指导临床管理实验结果：1. 相比于同龄健康人群,垂体ACTH腺瘤患者术前45RA+CD4+T细胞的比例和绝对计数、NaiveCD4+T细胞的比例及绝对计数均明显降低；CD38+CD8+T细胞的比例和绝对计数、DR+CD8+T细胞的比例和绝对计数均明显升高。垂体ACTH腺瘤患者免疫功能性别差异的显著性消失。2. 垂体ACTH腺瘤患者与无功能腺瘤具有显著的免疫学差异3. 手术治疗能够在短期改善垂体ACTH腺瘤患者的免疫功能4. 垂体ACTH腺瘤患者的血总皮质醇水平及ACTH水平与多项免疫功能指标相关5. 垂体ACTH腺瘤患者在围手术期易并发各类感染,CD8+CD38+T%及CD4绝对计数对于感染的防控、治疗有一定的意义实验结论：垂体ACTH腺瘤是一类具有鲜明免疫学特色的独特的垂体腺瘤,主要表现为纯真亚群的显著抑制和激活亚群的病态激活。垂体ACTH腺瘤患者整体免疫水平处于抑制状态,在围手术期易并发感染,其免疫状态与内分泌水平密切相关,手术治疗能全面解除免疫抑制状态,而围手术期监控免疫指标能够对临床管理可以起到指导的作用。
[Abstract]:Abstract : Pituitary adenoma is the most common cause of pituitary adenoma . The incidence of pituitary adenoma is the most common cause of pituitary adenoma , and the incidence of pituitary ACTH - dependent adenoma is the most common cause of pituitary ACTH - dependent adenoma .
To investigate the potential immunological mechanism of pituitary ACTH adenoma development , development and recurrence ;
To explore the effect of operation on immune function of pituitary ACTH adenoma patients .
To guide the management of perioperative management and reduce the incidence of infection . Methods : The immunological aspects of peripheral blood samples were collected : 11 levels of lymphocyte subsets were detected before and after operation by flow cytometry .
The levels of serum cortisol , 24 - hour urine free cortisol and ACTH in patients with pituitary ACTH adenoma were measured by detecting immunoglobulin - 3 ( IgG , IgA , IgM ) in order to assess humoral immunity . Objective To investigate the immune function of pituitary ACTH adenoma patients before and after operation , and to understand the status and characteristics of immune function in patients with pituitary ACTH adenoma .
2 . To investigate the immunological function of pituitary ACTH adenoma in pituitary adenoma by detecting and comparing the preoperative immunological parameters of pituitary ACTH adenoma patients and patients with pituitary adenoma .
3 . The effects of operation on immune function of pituitary ACTH adenoma were investigated by detecting and counting the changes of immunological indexes before and after operation in experimental group ( pituitary ACTH adenoma patients ) and control group ( patients with pituitary adenoma ) .
4 . To explore the relationship and influence between the immune indexes and endocrine indexes of the corresponding pituitary ACTH adenoma patients ;
5 . To collate and count cases of pituitary ACTH adenoma infection in perioperative period to seek clinical management experimental results from immunology : 1 . Compared with the healthy population of the same age , the proportion and absolute count of 45 RA + CD4 + T cells in the patients with pituitary ACTH adenoma were significantly decreased .
The ratio of CD38 + CD8 + T cells and absolute count , the ratio of DR + CD8 + T cells and the absolute count were significantly increased . There was a significant difference in immunology between pituitary ACTH - secreting adenoma and non - functional adenoma . Surgical treatment can improve the immune function of pituitary ACTH adenoma in the short term . The plasma cortisol level and ACTH level in pituitary ACTH adenoma patients were related to multiple immune function indexes . Pituitary ACTH adenoma is a kind of unique pituitary adenoma with distinct immunological characteristics .
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R736.4

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