中枢敏化和脑源性神经营养因子与原发痛经和内异症疼痛关系的研究
发布时间：2018-09-12 09:29
【摘要】：第一部分原发痛经对静息态脑网络功能及脑灰质体积的影响目的首次应用静息态功能磁共振(functional magnetic resonance imaging, fMRI)技术,在月经期采集重度原发痛经患者与健康对照女性的fMRI数据,观察长期重度痛经患者是否存在大脑结构和功能的改变,希望能从疼痛相关的中枢神经系统机制入手探索痛经的发病机制,为指导临床治疗,寻找新的治疗靶点提供科学的理论依据。方法招募10名重度原发痛经患者和10名健康育龄期女性。应用Philips 3.OT磁共振扫描仪采集受试者月经期静息态fMRI及高分辨结构像数据。采用基于Matlab2012平台的REST工具包,在灰质范围内分析2组受试者低频振幅统计图的差异。采用基于Matlab R2011b平台的GIFT软件进行独立成分分析,提取2个静息态脑网络：默认网络前部和后部。采用SPM8软件内的基于体素的形态学分析对高分辨结构像进行分割、空间标准化及平滑。应用SPM8进行统计分析,对比重度痛经和正常对照组在2个静息态脑网络内部的脑功能连接及全脑灰质体积差异。结果20名受试者均得到合格的静息态fMRI数据。(1)月经期全脑及局部脑区灰质体积在重度原发痛经组与健康对照组之间未见明显差异。(2)与健康对照组相比,重度痛经组在经期疼痛状态下左侧楔前叶活动增强,而双侧内侧前额叶活动减弱。(3)重度痛经组默认网络前部的左侧前额叶功能连接明显增加,而默认网络后部的右侧第一躯体感觉皮质功能连接明显减低。结论重度原发痛经患者在经期疼痛状态下部分与疼痛相关的脑区存在静息态功能和脑网络功能连接的改变。中枢敏化可能参与原发痛经的发生和发展。长期痛经患者脑区功能的改变可能出现在结构变化之前。第二部分脑源性神经营养因子与子宫内膜异位症疼痛关系的研究目的通过比较疼痛和无疼痛子宫内膜异位症患者异位病灶及在位内膜中脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)和特异性神经纤维标记物蛋白基因产物9.5 (protein gene product 9.5, PGP9.5)的分布和表达情况,探讨BDNF与内异症发病及疼痛的关系。材料与方法收集2014年10月至2015年9月期间于北京协和医院妇产科住院手术并经病理确诊为卵巢型内异症和单纯子宫肌瘤患者的异位和在位内膜,各25例。应用免疫组化方法检测卵巢型内异症患者(疼痛组13例,无疼痛组12例)的异位和在位内膜以及单纯肌瘤且不伴疼痛患者的子宫内膜中BDNF和PGP 9.5的分布和表达情况,分析其与内异症发生和疼痛症状的相关性。结果两组患者在年龄,孕产次方面无统计学差异。首次发现BDNF染色阳性区域位于内膜的上皮和间质,且上皮中的表达量明显高于间质。BDNF勺表达水平在非内异症患者在位内膜的增殖期和分泌期之间未见明显差异。BDNF在内异症卵巢病灶中的表达水平明显高于其在位内膜,同时,在内异症在位内膜中的表达水平也明显高于非内异症在位内膜。疼痛与无疼痛内异症患者异位和在位内膜中的BDNF表达水平未见明显差异。卵巢异位病灶内未见PGP9.5染色阳性,而内异症在位内膜中PGP9.5的阳性率高于非内异症在位内膜(20%vs.8%,P0.05)。结论研究首次明确了BDNF在子宫内膜异位症异位和在位内膜的上皮和间质中表达,且表达水平高于非内异症在位内膜,提示BDNF可能参与内异症的发生和发展。第三部分子宫肌瘤剔除术后意外发现子宫肉瘤患者的临床特点及治疗经验目的评估子宫肌瘤剔除术后意外发现子宫肉瘤的发生率以及电动肌瘤粉碎器的使用对隐匿性子宫肉瘤患者临床预后的影响。方法回顾性分析2009年1月至2013年12月期间于北京协和医院妇产科行子宫肌瘤剔除术后意外发现为子宫肉瘤患者的临床病历资料,分析其临床特点以及肌瘤粉碎器的使用对临床预后的影响。结果5年间共有4248例患者行子宫肌瘤剔除术,其中9例(0.21%)患者意外发现为子宫肉瘤,包括1例(0.02%)子宫平滑肌肉瘤和8例(0.19%)子宫内膜间质肉瘤。在3068例应用肌瘤粉碎器完成腹腔镜肌瘤剔除术的患者中意外发现5例(0.16%)子宫肉瘤,在1180例行开腹肌瘤剔除术的患者中意外发现4例(0.34%)子宫肉瘤,两组意外发现子宫肉瘤的发生率无统计学差异(P0.05)。9例肉瘤患者均存活,腹腔镜手术组和开腹手术组分别随访31.20个月和40.50个月。结论子宫肌瘤剔除术后意外发现为子宫肉瘤的总体发生率较低。目前对隐匿性子宫肉瘤应用肌瘤粉碎器后,在短期内似乎不会额外增加肉瘤播散的风险。
[Abstract]:Part I Effect of Primary Dysmenorrhea on Resting State Brain Network Function and Gray Matter Volume Objective To collect fMRI data of severe primary dysmenorrhea patients and healthy control women during menstrual period by resting state functional magnetic resonance imaging (fMRI) for the first time to observe whether there is brain in patients with long-term severe dysmenorrhea. The changes of structure and function were expected to explore the pathogenesis of dysmenorrhea from the pain-related central nervous system mechanism and provide scientific theoretical basis for guiding clinical treatment and finding new therapeutic targets.Methods 10 patients with severe primary dysmenorrhea and 10 healthy women of childbearing age were recruited. Using REST toolkit based on MATLAB 2012 platform, the differences of low-frequency amplitude statistics between two groups of subjects were analyzed in the gray matter range. GIFT software based on MATLAB R2011b platform was used for independent component analysis to extract two resting brain networks: the front and back of default network. Voxel-based morphological analysis in SPM8 software was used to segment, standardize and smooth high-resolution structural images. SPM8 was used for statistical analysis to compare the functional connectivity of brain and the volume difference of gray matter between severe dysmenorrhea and normal control group. (2) In severe dysmenorrhea group, the activity of left anterior cuneate lobe was increased, while the activity of bilateral medial prefrontal lobe was decreased in severe dysmenorrhea group. (3) In severe dysmenorrhea group, the volume of gray matter in whole brain and local brain regions was not significantly different between severe primary dysmenorrhea group and healthy control group. The functional connectivity of left prefrontal lobe was significantly increased, while the functional connectivity of right first somatosensory cortex was significantly decreased in the posterior part of default network. The changes of brain function in patients with chronic dysmenorrhea may occur before structural changes. Part II The relationship between brain-derived neurotrophic factors and pain in endometriosis Distribution and expression of BDNF and protein gene product 9.5 (PGP9.5) were investigated to investigate the relationship between BDNF and endometriosis and pain. The distribution and expression of BDNF and PGP 9.5 in ectopic and eutopic endometrium of patients with ovarian endometriosis (13 cases in pain group, 12 cases in pain-free group) and endometrium of patients with simple myoma without pain were detected by immunohistochemistry. Results There was no significant difference between the two groups in age, pregnancy and parity. For the first time, BDNF positive areas were found in the epithelium and stroma of endometrium, and the expression of BDNF spoon was significantly higher than that of stroma. The expression level of BDNF in eutopic and eutopic endometrium of endometriosis was significantly higher than that of non-endometriosis. The expression level of BDNF in ectopic and eutopic endometrium of patients with painful and non-painful endometriosis was not significantly different. No PGP 9.5 staining was found in eutopic endometrium of endometriosis, but the positive rate of PGP 9.5 in eutopic endometrium of endometriosis was higher than that in eutopic endometrium of non-endometriosis (20% vs. 8%, P 0.05). Objective To evaluate the incidence of unexpected uterine sarcoma after myomectomy and the effect of electromyomectomy on the clinical prognosis of patients with occult uterine sarcoma. Objective To analyze the clinical data of patients with uterine sarcoma accidentally discovered after myomectomy in Peking Union Medical College Hospital from January 2009 to December 2013. 21% of the patients were unexpectedly diagnosed as uterine sarcoma, including 1 (0.02%) leiomyosarcoma and 8 (0.19%) endometrial stromal sarcoma. There was no significant difference in the incidence of uterine sarcoma between the two groups (P 0.05). Nine patients with uterine sarcoma survived. The patients in the laparoscopic group and the open group were followed up for 31.20 months and 40.50 months, respectively. The smashing device does not seem to increase the risk of sarcoma dissemination in the short term.
【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】：R711.51
[Abstract]:Part I Effect of Primary Dysmenorrhea on Resting State Brain Network Function and Gray Matter Volume Objective To collect fMRI data of severe primary dysmenorrhea patients and healthy control women during menstrual period by resting state functional magnetic resonance imaging (fMRI) for the first time to observe whether there is brain in patients with long-term severe dysmenorrhea. The changes of structure and function were expected to explore the pathogenesis of dysmenorrhea from the pain-related central nervous system mechanism and provide scientific theoretical basis for guiding clinical treatment and finding new therapeutic targets.Methods 10 patients with severe primary dysmenorrhea and 10 healthy women of childbearing age were recruited. Using REST toolkit based on MATLAB 2012 platform, the differences of low-frequency amplitude statistics between two groups of subjects were analyzed in the gray matter range. GIFT software based on MATLAB R2011b platform was used for independent component analysis to extract two resting brain networks: the front and back of default network. Voxel-based morphological analysis in SPM8 software was used to segment, standardize and smooth high-resolution structural images. SPM8 was used for statistical analysis to compare the functional connectivity of brain and the volume difference of gray matter between severe dysmenorrhea and normal control group. (2) In severe dysmenorrhea group, the activity of left anterior cuneate lobe was increased, while the activity of bilateral medial prefrontal lobe was decreased in severe dysmenorrhea group. (3) In severe dysmenorrhea group, the volume of gray matter in whole brain and local brain regions was not significantly different between severe primary dysmenorrhea group and healthy control group. The functional connectivity of left prefrontal lobe was significantly increased, while the functional connectivity of right first somatosensory cortex was significantly decreased in the posterior part of default network. The changes of brain function in patients with chronic dysmenorrhea may occur before structural changes. Part II The relationship between brain-derived neurotrophic factors and pain in endometriosis Distribution and expression of BDNF and protein gene product 9.5 (PGP9.5) were investigated to investigate the relationship between BDNF and endometriosis and pain. The distribution and expression of BDNF and PGP 9.5 in ectopic and eutopic endometrium of patients with ovarian endometriosis (13 cases in pain group, 12 cases in pain-free group) and endometrium of patients with simple myoma without pain were detected by immunohistochemistry. Results There was no significant difference between the two groups in age, pregnancy and parity. For the first time, BDNF positive areas were found in the epithelium and stroma of endometrium, and the expression of BDNF spoon was significantly higher than that of stroma. The expression level of BDNF in eutopic and eutopic endometrium of endometriosis was significantly higher than that of non-endometriosis. The expression level of BDNF in ectopic and eutopic endometrium of patients with painful and non-painful endometriosis was not significantly different. No PGP 9.5 staining was found in eutopic endometrium of endometriosis, but the positive rate of PGP 9.5 in eutopic endometrium of endometriosis was higher than that in eutopic endometrium of non-endometriosis (20% vs. 8%, P 0.05). Objective To evaluate the incidence of unexpected uterine sarcoma after myomectomy and the effect of electromyomectomy on the clinical prognosis of patients with occult uterine sarcoma. Objective To analyze the clinical data of patients with uterine sarcoma accidentally discovered after myomectomy in Peking Union Medical College Hospital from January 2009 to December 2013. 21% of the patients were unexpectedly diagnosed as uterine sarcoma, including 1 (0.02%) leiomyosarcoma and 8 (0.19%) endometrial stromal sarcoma. There was no significant difference in the incidence of uterine sarcoma between the two groups (P 0.05). Nine patients with uterine sarcoma survived. The patients in the laparoscopic group and the open group were followed up for 31.20 months and 40.50 months, respectively. The smashing device does not seem to increase the risk of sarcoma dissemination in the short term.
【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】：R711.51
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