青少年肥胖中枢机制及针灸治疗的神经影像学及动物模型研究
发布时间：2018-08-13 21:03
【摘要】：第一部分食物与食欲相关fMRI研究的Meta分析 目的确认大脑功能区对食物刺激反应的一致性,借以探讨中枢对饥饿状态及含不同热量食物反应的调节机制。方法应用SDM体素Meta分析法对正常体重受试者fMRI数据进行分析,分析内容包括：食物与非食物刺激下脑区兴奋性的差异；饥饿状态下的中枢调节；不同热量食物刺激对中枢的影响。结果1.与非食物图片相比,食物图片刺激时具有较强激活的脑区包括：双侧后梭状回,左外侧眶额回及左侧中间岛叶；2.饥饿状态下,影响中枢调节的脑区包括：右侧杏仁核,左外侧眶额回；3.不同热量食物刺激影响的脑区包括：下丘脑及腹侧纹状体。局限性综合上述的结果,脑区激活的一致性仅在中等水平,这意味着实验方法对结果仍存在诸多的影响；此外,其它的脑区仍可能参与食欲及食物刺激的中枢调节。结论降低梭状回,眶额回,杏仁核,下丘脑及腹侧纹状体的兴奋水平可能抑制食欲。 第二部分针灸减肥治疗对肥胖青少年中枢神经系统的影响 目的应用fMRI及DARTEL-VBM分析方法探讨针灸减肥对肥胖青少年中枢神经系统的影响。方法10名单纯性肥胖青少年(男7,女3,14～18岁,右利手,体重指数：29.03±4.81kg/m2)行阶段性针灸减肥治疗,在治疗前、后分别行颅脑高分辨三维T1加权成像及fMRI扫描；同时招募10名年龄和性别相匹配的健康自愿者(右利手,体重指数：25.05±5.02kg/m2)作为对照组。fMRI方案：观察受试者在接受食物图片视觉刺激后的中枢反应,然后用手法针灸左侧足三里(ST36)及右侧丰隆(ST40)的同时,再进行一次同样的fMRI扫描。DARTEL-VBM分析：对比受试者接受阶段性治疗前后大脑灰白质体积差异。数据分析使用基于MATLAB R2009a的SPM8软件.结果1.与非食物图片视觉刺激相比,肥胖儿童接受食物图片视觉刺激后脑干、左侧丘脑、双侧眶额皮质、岛叶皮质、海马及海马旁回、后扣带回、楔前叶、小脑以及枕叶等多个脑区明显激活；2.与针灸前相比,针灸后接受食物图片视觉刺激时,脑干、双侧眶额皮质、岛叶皮质、后扣带回、枕叶及左侧小脑的激活明显受抑制；3. DARTEL-VBM结果：右侧额上回,小脑后叶椎体灰质体积减小,右侧中央前回灰质体积增大；左侧海马旁区梭状回,桥脑及中央前回区白质体积减小；右侧楔前叶白质体积增大；4.治疗前肥胖受试者与体重正常对照组比较,小脑及外侧苍白球灰质体积增大,桥脑及小脑白质体积减小；治疗后肥胖受试者与体重正常对照组比较,外侧苍白球灰质体积显著增大,桥脑白质体积增大,原先位于小脑的灰质及白质差异区未显现。结论针灸减肥疗法不仅能够对中枢产生短时的影响,并有可能导致皮层的重建；正常体重者与肥胖者间可能存在大脑细微结构的差异。 第三部分应用中枢神经影像学及免疫组化的方法研究肥胖模型大鼠 目的应用肥胖动物模型进一步深入研究肥胖发生的中枢机制以及针灸减肥的作用机理。方法利用高脂饲料诱导SD大鼠,构建肥胖模型动物。最终成模11只(雌性6只)。15只大鼠作为正常体重对照组。应用静息态功能磁共振及扩散张量成像手段对鼠脑成像并分析。同时,应用针灸疗法治疗肥胖大鼠,并通过对大鼠腹部脂肪体积测定来确认针灸疗法的作用。研究末期,将大鼠处死并取脑及肝脏组织进行病理及免疫组化的研究。结果1.针灸减肥疗法能有效减低肥胖大鼠的体重,并降低大鼠腹腔内脂肪的比例(P0.05)；2.大鼠神经影像学的研究发现,肥胖大鼠与正常体重对照组在多个感兴趣区存在功能差异；静息态fMRI结果,肥胖组大鼠双侧海马及右侧中丘脑较活跃,枕叶皮层活跃度较低；而针灸疗法能使大鼠的双侧嗅球,额叶皮层、右侧岛叶及海马活跃增强,而右侧丘脑活跃度减低；3.DTI从另一个角度研究大鼠脑功能差异；肥胖鼠桥脑、嗅球及杏仁核部分DTI参数与对照组存在差异(P0.05)。桥脑可能存在性别差异；在对影响肥胖发生因素的logistic回归分析中,年龄、纤维束的ADC (apparent diffusion coefficient,表观扩散系数)值及感兴趣区的FA(Fraction Anisotropy,分数各向异性)值与肥胖的发生呈正相关；4.大鼠肝脏病理组织的分析,提示针灸治疗对内脏脂质的分布可能存在影响；脑区免疫组化分析发现,不同脑区的神经递质染色程度不同；肥胖大鼠部分脑区递质染色程度与对照组相异。肥胖组杏仁核及海马较对照组有较高的5-HT染色,在岛叶及桥/小脑对照组5-HT染色更高；瘦素染色程度较低,肥胖组桥小脑区域染色程度较对照组高,对照组在岛叶也存在5-HT染色；神经肽Y在肥胖组的染色程度较对照组高；接受针灸治疗的肥胖大鼠较未接受针灸治疗的肥胖大鼠,各脑区三种神经递质染色程度增强。结论肥胖的发生与神经中枢的功能异常以及解剖、生理基础存在关联；针灸减肥法可能存在分子水平的作用机制。
[Abstract]:Part 1 Meta analysis of food and appetite related fMRI research
Objective To confirm the consistency of food stimulation response in brain functional areas and to explore the regulatory mechanism of central nervous system on starvation and food with different calories. Results 1. Compared with non-food pictures, food pictures showed stronger activation in bilateral posterior fusiform gyrus, left lateral orbital frontal gyrus and left middle insula; 2. Under starvation, the brain regions that affected central regulation included right amygdala and left middle insula. Lateral orbital frontal gyrus; 3. The brain regions affected by different caloric food stimuli include hypothalamus and ventral striatum. Conclusion Reducing excitatory levels in the fusiform gyrus, orbital frontal gyrus, amygdala, hypothalamus and ventral striatum may inhibit appetite.
The second part is the effect of acupuncture and obesity therapy on central nervous system in obese adolescents.
Objective To investigate the effect of acupuncture and moxibustion on central nervous system in obese adolescents by using fMRI and DARTEL-VBM. Methods 10 obese adolescents (male 7, female 3, 14-18 years old, right-handed, body mass index 29.03 +4.81kg/m2) were treated with acupuncture and moxibustion at different stages. Before and after treatment, high-resolution three-dimensional T1-weighted imaging and f-weighted imaging were performed respectively. MRI scans were performed in 10 age-and sex-matched healthy volunteers (right-handed, BMI: 25.05.02 kg/m2) as control group. The fMRI regimen was designed to observe the central response to visual stimulation of food pictures, followed by manipulative acupuncture of left-foot 36 (ST36) and right-foot Fenglong (ST40). Similar fMRI scans. DARTEL-VBM analysis: Compare the volume differences of gray matter before and after phased treatment. Data were analyzed using SPM8 software based on MATLAB R2009a. Results 1. Obese children received visual stimulation of food pictures after brainstem, left thalamus, bilateral orbital frontal cortex, insular cortex compared with non-food pictures. The activation of brain stem, bilateral orbital frontal cortex, insular cortex, posterior cingulate gyrus, posterior cingulate gyrus, anterior cuneiform lobe, cerebellum and occipital lobe was significantly inhibited after acupuncture compared with that before acupuncture. The volume of gray matter in the posterior lobe of cerebellum decreased and that in the right anterior central gyrus increased; the volume of white matter in the left parahippocampal fusiform gyrus, pons and anterior central gyrus decreased; the volume of white matter in the right anterior cuneate increased; 4. The volume of gray matter in the cerebellum and lateral pallidus increased, pons and small compared with the normal weight control group before treatment. After treatment, the volume of gray matter in the lateral globus pallidus increased significantly, and the volume of white matter in pons increased significantly, but the difference between gray matter and white matter in cerebellum did not appear. There may be differences in fine structure between normal weight and obese people.
The third part is to study the obesity model rats by central nervous imaging and immunohistochemistry.
Objective To further study the central mechanism of obesity and the mechanism of acupuncture and moxibustion in reducing weight in obese animal models.Methods SD rats were induced by high-fat diet. At the end of the study, rats were sacrificed and their brain and liver tissues were taken for pathological and immunohistochemical studies. Results 1. Acupuncture and moxibustion therapy could effectively reduce the body weight of obese rats. The ratio of intraperitoneal fat in rats was also decreased (P 0.05). 2. Neuroimaging study showed that there were functional differences between obese rats and normal weight control group in multiple regions of interest; resting state fMRI results showed that bilateral hippocampus and right middle thalamus were more active in obese rats, and occipital cortex was less active in obese rats; and acupuncture and moxibustion therapy could make the rats have lower occipital cortex activity. The activity of bilateral olfactory bulb, frontal cortex, right insular lobe and hippocampus increased, but the activity of right thalamus decreased. 3. DTI study the difference of brain function in rats from another point of view; DTI parameters of pons, olfactory bulb and amygdala in obese rats were different from those in control group (P In istic regression analysis, age, ADC (apparent diffusion coefficient) and FA (Fraction Anisotropy) in the area of interest (ROI) were positively correlated with the occurrence of obesity. 4. Pathological analysis of rat liver suggested that acupuncture treatment might have an effect on the distribution of visceral lipids. Immunohistochemical analysis showed that neurotransmitter staining was different in different brain regions; neurotransmitter staining was different in some brain regions of obese rats compared with the control group. The staining degree of neuropeptide Y in obesity group was higher than that in control group, and the staining degree of three neurotransmitters in each brain area of obese rats treated with acupuncture was higher than that of obese rats not treated with acupuncture. There is a correlation between physiological basis and acupuncture.
【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】：2013
【分类号】：R445.2;R589.2
本文编号：2182181
[Abstract]:Part 1 Meta analysis of food and appetite related fMRI research
Objective To confirm the consistency of food stimulation response in brain functional areas and to explore the regulatory mechanism of central nervous system on starvation and food with different calories. Results 1. Compared with non-food pictures, food pictures showed stronger activation in bilateral posterior fusiform gyrus, left lateral orbital frontal gyrus and left middle insula; 2. Under starvation, the brain regions that affected central regulation included right amygdala and left middle insula. Lateral orbital frontal gyrus; 3. The brain regions affected by different caloric food stimuli include hypothalamus and ventral striatum. Conclusion Reducing excitatory levels in the fusiform gyrus, orbital frontal gyrus, amygdala, hypothalamus and ventral striatum may inhibit appetite.
The second part is the effect of acupuncture and obesity therapy on central nervous system in obese adolescents.
Objective To investigate the effect of acupuncture and moxibustion on central nervous system in obese adolescents by using fMRI and DARTEL-VBM. Methods 10 obese adolescents (male 7, female 3, 14-18 years old, right-handed, body mass index 29.03 +4.81kg/m2) were treated with acupuncture and moxibustion at different stages. Before and after treatment, high-resolution three-dimensional T1-weighted imaging and f-weighted imaging were performed respectively. MRI scans were performed in 10 age-and sex-matched healthy volunteers (right-handed, BMI: 25.05.02 kg/m2) as control group. The fMRI regimen was designed to observe the central response to visual stimulation of food pictures, followed by manipulative acupuncture of left-foot 36 (ST36) and right-foot Fenglong (ST40). Similar fMRI scans. DARTEL-VBM analysis: Compare the volume differences of gray matter before and after phased treatment. Data were analyzed using SPM8 software based on MATLAB R2009a. Results 1. Obese children received visual stimulation of food pictures after brainstem, left thalamus, bilateral orbital frontal cortex, insular cortex compared with non-food pictures. The activation of brain stem, bilateral orbital frontal cortex, insular cortex, posterior cingulate gyrus, posterior cingulate gyrus, anterior cuneiform lobe, cerebellum and occipital lobe was significantly inhibited after acupuncture compared with that before acupuncture. The volume of gray matter in the posterior lobe of cerebellum decreased and that in the right anterior central gyrus increased; the volume of white matter in the left parahippocampal fusiform gyrus, pons and anterior central gyrus decreased; the volume of white matter in the right anterior cuneate increased; 4. The volume of gray matter in the cerebellum and lateral pallidus increased, pons and small compared with the normal weight control group before treatment. After treatment, the volume of gray matter in the lateral globus pallidus increased significantly, and the volume of white matter in pons increased significantly, but the difference between gray matter and white matter in cerebellum did not appear. There may be differences in fine structure between normal weight and obese people.
The third part is to study the obesity model rats by central nervous imaging and immunohistochemistry.
Objective To further study the central mechanism of obesity and the mechanism of acupuncture and moxibustion in reducing weight in obese animal models.Methods SD rats were induced by high-fat diet. At the end of the study, rats were sacrificed and their brain and liver tissues were taken for pathological and immunohistochemical studies. Results 1. Acupuncture and moxibustion therapy could effectively reduce the body weight of obese rats. The ratio of intraperitoneal fat in rats was also decreased (P 0.05). 2. Neuroimaging study showed that there were functional differences between obese rats and normal weight control group in multiple regions of interest; resting state fMRI results showed that bilateral hippocampus and right middle thalamus were more active in obese rats, and occipital cortex was less active in obese rats; and acupuncture and moxibustion therapy could make the rats have lower occipital cortex activity. The activity of bilateral olfactory bulb, frontal cortex, right insular lobe and hippocampus increased, but the activity of right thalamus decreased. 3. DTI study the difference of brain function in rats from another point of view; DTI parameters of pons, olfactory bulb and amygdala in obese rats were different from those in control group (P In istic regression analysis, age, ADC (apparent diffusion coefficient) and FA (Fraction Anisotropy) in the area of interest (ROI) were positively correlated with the occurrence of obesity. 4. Pathological analysis of rat liver suggested that acupuncture treatment might have an effect on the distribution of visceral lipids. Immunohistochemical analysis showed that neurotransmitter staining was different in different brain regions; neurotransmitter staining was different in some brain regions of obese rats compared with the control group. The staining degree of neuropeptide Y in obesity group was higher than that in control group, and the staining degree of three neurotransmitters in each brain area of obese rats treated with acupuncture was higher than that of obese rats not treated with acupuncture. There is a correlation between physiological basis and acupuncture.
【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】：2013
【分类号】：R445.2;R589.2
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