【摘要】：第一部分食物與食欲相關(guān)fMRI研究的Meta分析 目的確認(rèn)大腦功能區(qū)對(duì)食物刺激反應(yīng)的一致性,借以探討中樞對(duì)饑餓狀態(tài)及含不同熱量食物反應(yīng)的調(diào)節(jié)機(jī)制。方法應(yīng)用SDM體素Meta分析法對(duì)正常體重受試者fMRI數(shù)據(jù)進(jìn)行分析,分析內(nèi)容包括：食物與非食物刺激下腦區(qū)興奮性的差異；饑餓狀態(tài)下的中樞調(diào)節(jié)；不同熱量食物刺激對(duì)中樞的影響。結(jié)果1.與非食物圖片相比,食物圖片刺激時(shí)具有較強(qiáng)激活的腦區(qū)包括：雙側(cè)后梭狀回,左外側(cè)眶額回及左側(cè)中間島葉；2.饑餓狀態(tài)下,影響中樞調(diào)節(jié)的腦區(qū)包括：右側(cè)杏仁核,左外側(cè)眶額回；3.不同熱量食物刺激影響的腦區(qū)包括：下丘腦及腹側(cè)紋狀體。局限性綜合上述的結(jié)果,腦區(qū)激活的一致性僅在中等水平,這意味著實(shí)驗(yàn)方法對(duì)結(jié)果仍存在諸多的影響；此外,其它的腦區(qū)仍可能參與食欲及食物刺激的中樞調(diào)節(jié)。結(jié)論降低梭狀回,眶額回,杏仁核,下丘腦及腹側(cè)紋狀體的興奮水平可能抑制食欲。 第二部分針灸減肥治療對(duì)肥胖青少年中樞神經(jīng)系統(tǒng)的影響 目的應(yīng)用fMRI及DARTEL-VBM分析方法探討針灸減肥對(duì)肥胖青少年中樞神經(jīng)系統(tǒng)的影響。方法10名單純性肥胖青少年(男7,女3,14～18歲,右利手,體重指數(shù)：29.03±4.81kg/m2)行階段性針灸減肥治療,在治療前、后分別行顱腦高分辨三維T1加權(quán)成像及fMRI掃描；同時(shí)招募10名年齡和性別相匹配的健康自愿者(右利手,體重指數(shù)：25.05±5.02kg/m2)作為對(duì)照組。fMRI方案：觀察受試者在接受食物圖片視覺刺激后的中樞反應(yīng),然后用手法針灸左側(cè)足三里(ST36)及右側(cè)豐隆(ST40)的同時(shí),再進(jìn)行一次同樣的fMRI掃描。DARTEL-VBM分析：對(duì)比受試者接受階段性治療前后大腦灰白質(zhì)體積差異。數(shù)據(jù)分析使用基于MATLAB R2009a的SPM8軟件.結(jié)果1.與非食物圖片視覺刺激相比,肥胖兒童接受食物圖片視覺刺激后腦干、左側(cè)丘腦、雙側(cè)眶額皮質(zhì)、島葉皮質(zhì)、海馬及海馬旁回、后扣帶回、楔前葉、小腦以及枕葉等多個(gè)腦區(qū)明顯激活；2.與針灸前相比,針灸后接受食物圖片視覺刺激時(shí),腦干、雙側(cè)眶額皮質(zhì)、島葉皮質(zhì)、后扣帶回、枕葉及左側(cè)小腦的激活明顯受抑制；3. DARTEL-VBM結(jié)果：右側(cè)額上回,小腦后葉椎體灰質(zhì)體積減小,右側(cè)中央前回灰質(zhì)體積增大；左側(cè)海馬旁區(qū)梭狀回,橋腦及中央前回區(qū)白質(zhì)體積減��；右側(cè)楔前葉白質(zhì)體積增大；4.治療前肥胖受試者與體重正常對(duì)照組比較,小腦及外側(cè)蒼白球灰質(zhì)體積增大,橋腦及小腦白質(zhì)體積減��；治療后肥胖受試者與體重正常對(duì)照組比較,外側(cè)蒼白球灰質(zhì)體積顯著增大,橋腦白質(zhì)體積增大,原先位于小腦的灰質(zhì)及白質(zhì)差異區(qū)未顯現(xiàn)。結(jié)論針灸減肥療法不僅能夠?qū)χ袠挟a(chǎn)生短時(shí)的影響,并有可能導(dǎo)致皮層的重建；正常體重者與肥胖者間可能存在大腦細(xì)微結(jié)構(gòu)的差異。 第三部分應(yīng)用中樞神經(jīng)影像學(xué)及免疫組化的方法研究肥胖模型大鼠 目的應(yīng)用肥胖動(dòng)物模型進(jìn)一步深入研究肥胖發(fā)生的中樞機(jī)制以及針灸減肥的作用機(jī)理。方法利用高脂飼料誘導(dǎo)SD大鼠,構(gòu)建肥胖模型動(dòng)物。最終成模11只(雌性6只)。15只大鼠作為正常體重對(duì)照組。應(yīng)用靜息態(tài)功能磁共振及擴(kuò)散張量成像手段對(duì)鼠腦成像并分析。同時(shí),應(yīng)用針灸療法治療肥胖大鼠,并通過對(duì)大鼠腹部脂肪體積測(cè)定來(lái)確認(rèn)針灸療法的作用。研究末期,將大鼠處死并取腦及肝臟組織進(jìn)行病理及免疫組化的研究。結(jié)果1.針灸減肥療法能有效減低肥胖大鼠的體重,并降低大鼠腹腔內(nèi)脂肪的比例(P0.05)；2.大鼠神經(jīng)影像學(xué)的研究發(fā)現(xiàn),肥胖大鼠與正常體重對(duì)照組在多個(gè)感興趣區(qū)存在功能差異；靜息態(tài)fMRI結(jié)果,肥胖組大鼠雙側(cè)海馬及右側(cè)中丘腦較活躍,枕葉皮層活躍度較低；而針灸療法能使大鼠的雙側(cè)嗅球,額葉皮層、右側(cè)島葉及海馬活躍增強(qiáng),而右側(cè)丘腦活躍度減低；3.DTI從另一個(gè)角度研究大鼠腦功能差異；肥胖鼠橋腦、嗅球及杏仁核部分DTI參數(shù)與對(duì)照組存在差異(P0.05)。橋腦可能存在性別差異；在對(duì)影響肥胖發(fā)生因素的logistic回歸分析中,年齡、纖維束的ADC (apparent diffusion coefficient,表觀擴(kuò)散系數(shù))值及感興趣區(qū)的FA(Fraction Anisotropy,分?jǐn)?shù)各向異性)值與肥胖的發(fā)生呈正相關(guān)；4.大鼠肝臟病理組織的分析,提示針灸治療對(duì)內(nèi)臟脂質(zhì)的分布可能存在影響；腦區(qū)免疫組化分析發(fā)現(xiàn),不同腦區(qū)的神經(jīng)遞質(zhì)染色程度不同；肥胖大鼠部分腦區(qū)遞質(zhì)染色程度與對(duì)照組相異。肥胖組杏仁核及海馬較對(duì)照組有較高的5-HT染色,在島葉及橋/小腦對(duì)照組5-HT染色更高；瘦素染色程度較低,肥胖組橋小腦區(qū)域染色程度較對(duì)照組高,對(duì)照組在島葉也存在5-HT染色；神經(jīng)肽Y在肥胖組的染色程度較對(duì)照組高；接受針灸治療的肥胖大鼠較未接受針灸治療的肥胖大鼠,各腦區(qū)三種神經(jīng)遞質(zhì)染色程度增強(qiáng)。結(jié)論肥胖的發(fā)生與神經(jīng)中樞的功能異常以及解剖、生理基礎(chǔ)存在關(guān)聯(lián)；針灸減肥法可能存在分子水平的作用機(jī)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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2013
【分類號(hào)】：R445.2;R589.2

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本文編號(hào)：2182181