【作者】 何春燕；

【导师】 王文健； 陈剑秋； 许得盛；

【作者基本信息】 复旦大学 ， 中西医结合临床， 2007， 博士

【摘要】 聚证学说是以气化障碍为核心的一种中医证候理论。聚证在正气虚弱(气化不足)的基础上由邪气乘虚留驻而成，以精微不得正常化生和布输为基本特征；治疗应以散聚法作为基本治法。本文在聚证学说指导下，对具有典型聚证证候的代谢综合征高危人群中心性肥胖患者脂肪餐后的代谢改变作了较深入的观察，以了解聚证患者气化障碍的代谢学基础，并对散聚法的作用和机理作了研究。目的1.以代谢综合征高危人群——中心性肥胖患者为研究对象，总结其临床证候特点，进一步规范聚证辨证，并结合实验室检测提出聚证微观辨证要点。2.观察中心性肥胖男性脂负荷下脂肪吸收过程，了解其餐后甘油三酯及游离脂肪酸代谢特点，评价其脂肪细胞能量储存功能。3.观察中心性肥胖男性胰岛素抵抗程度及相关脂肪细胞因子的表达，分析二者与餐后脂代谢紊乱的关系，并探讨正虚(气化不足)和邪实在聚证发生和发展中的作用。4.观察散聚法对中心性肥胖男性餐后脂代谢的作用，探讨相关作用机制，并观察散聚法对临床症状的作用，微观与宏观地验证聚证学说的科学性和适用性，完善和丰富聚证学说的理论框架和内涵。方法1.代谢综合征高危人群中医临床证候特点门诊收集病例，予简易口服葡萄糖耐量试验及一般检查筛选出空腹血糖正常、糖耐量试验正常且空腹血脂正常者，选择45例腰围≥90厘米、胰岛素抵抗指数≥1的中心性肥胖男性作为研究对象，观察其临床表现，记录常见症状，并按症状轻、中、重三级进行评分，比较症状出现的频率。2.代谢综合征高危人群餐后脂代谢特点研究对象：以上述45例肥胖男性为研究对象，并以30例非肥胖且胰岛素抵抗指数＜1的健康男性作为正常人群进行参照。脂肪负荷试验：予受试者口服总热量1100千卡的脂肪餐(含脂肪55％)，分别于空腹状态和进食后2、4、6、8小时抽取静脉血，动态监测受试者血甘油三酯(TG)、游离脂肪酸(FFA)、血糖及胰岛素水平变化情况。一般状况检查：量取受试者身高、体重、腰围、臀围、收缩压与舒张压，计算体重指数、腰臀比和胰岛素抵抗指数(HOMA2-IR)，并分析这几者与餐后脂代谢的相关性。检测受试者其它血脂水平，包括总胆固醇(TC)、低密度脂蛋白-胆固醇(LDL-c)、高密度脂蛋白.胆固醇(HDL-c)和脂蛋白-a水平。3.代谢综合征高危人群相关脂肪细胞因子的表达相关脂肪细胞因子的检测：选择上述45例中心性肥胖男性和30例非肥胖健康男性，抽取静脉血，采用酶联免疫吸附法(ELISA)分别检测血清脂联素、瘦素、C反应蛋白(CRP)、白介素-6(1L-6)、肿瘤坏死因子-α(TNF-α)及血浆中纤溶酶原激活物抑制物-1(PAI-1)、组织型纤溶酶原激活物(t-PA)的含量。相关性分析：分别采用简单线性相关分析和多元逐步回归分析法，分析上述细胞因子之间的关联及与机体肥胖程度和胰岛素抵抗的相关性，并分析细胞因子与餐后脂代谢的相关性。4.散聚法对代谢综合征高危人群餐后脂代谢的作用及机制散聚法对代谢综合征高危人群餐后脂代谢的作用：采取随机、单盲、安慰剂对照研究方法，将45例中心性肥胖男性随机分为中药组和安慰剂组，分别接受中药益气散聚方和安慰剂10周的干预治疗。观察期间不改变原生活方式。治疗前、后予脂肪负荷试验，观察治疗前后两组脂肪餐后TG、FFA、血糖及胰岛素各时相的变化情况，比较两组间治疗前后差异。并以30例健康男性作为正常对照，比较肥胖男性治疗后脂代谢改善情况。散聚法对代谢综合征高危人群一般状况的影响：设中药组和安慰剂组，观察治疗前后受试者腰围、臀围、体重、血压的变化及TC、LDL-c、HDL-c和脂蛋白-a等其它血脂的改变，比较治疗前后体重指数、胰岛素抵抗指数的差异。并以健康男性为正常对照，比较肥胖男性治疗后一般状况的改善程度。散聚法对代谢综合征高危人群相关脂肪细胞因子表达的影响：设中药组和安慰剂组，观察治疗前后脂联素、瘦素、CRP、TNF-α、IL-6及血浆中PAI-1、t-PA水平的变化，并以健康男性为正常对照，比较肥胖男性治疗后细胞因子水平情况。散聚法对代谢综合征高危人群临床表现的作用：设中药组和安慰剂组，观察治疗前后各临床症状评分改变情况。结果1.代谢综合征高危人群中医证候特点中心性肥胖男性临床证候呈现虚实夹杂之象，其中出现频率最高的临床症状依次为：体形肥胖、肢体困重、气短乏力、自汗、脘腹痞满；并伴有头晕、胸闷、肢体麻木、纳差、口臭口苦、大便干结或稀溏、尿黄赤及失眠多梦等其它症状。舌包括有正常舌、舌体淡胖、边有齿痕印、舌质红等；舌苔包括有薄白苔、白腻苔、黄腻苔、厚腻苔、少苔等；脉象包括有平脉、弦脉、弦数脉、滑脉、细数脉、洪大脉、濡细脉和沉脉等。体形肥胖的出现率明显高于气短乏力、自汗和脘腹痞满；肢体困重的出现率明显高于自汗和脘腹痞满；气短乏力的出现率高于脘腹痞满。2.代谢综合征高危人群餐后脂代谢特点代谢综合征高危人群餐后甘油三酯、游离脂肪酸代谢特点：肥胖男性和健康男性空腹血TG浓度无明显差异，但脂肪餐后从第2小时起肥胖男性TG浓度均较健康男性有明显升高(P＜0.01)。健康男性TG峰值出现在第4小时，而肥胖患者TG峰值明显延迟出现。健康男性第8小时TG浓度接近其空腹TG水平，而肥胖男性第8小时TG浓度明显高于其空腹TG水平(P＜0.001)，提示TG清除减慢。肥胖男性甘油三酯曲线下面积(TGAUC)及甘油三酯峰反应(TGPR)均明显高于健康男性。空腹及脂肪餐后第2、6、8小时肥胖男性血FFA浓度明显高于健康男性(P＜0.05)，第4小时肥胖男性和健康男性血FFA浓度无统计学差异。肥胖患者在第6小时FFA继续升高，与第4小时有明显差异(P＜0.05)，而健康男性第6小时与第4小时相比FFA浓度无统计学差异。第8小时健康男性FFA明显下降，肥胖患者FFA浓度呈下降趋势，但与第6小时无统计学差异。代谢综合征肥胖高危人群餐后血糖、胰岛素代谢特点：肥胖男性与健康男性空腹血糖水平无明显差异，脂肪餐后2小时肥胖男性血糖水平较健康男性有明显升高(P＜0.01)，第4小时亦高于健康志愿者(P＜0.05)，第6小时两组血糖水平无明显差异。空腹及脂肪餐后第2小时肥胖男性血胰岛素水平高于健康男性(P＜0.001)。第4、6、8小时肥胖男性胰岛素水平与健康男性无明显差异。餐后第4小时起，二者血胰岛素水平开始明显下降，至第8小时两者血胰岛素水平与其空腹水平接近。代谢综合征肥胖高危人群一般状况：肥胖男性的体重指数、腰围及腰臀比明显高于健康男性(P均＜0.001)，HOMA2-IR也与健康男性有显著差异(P＜0.001)。肥胖患者收缩压高出健康志愿者约7mmHg，差异有统计学意义(P＜0.05)。肥胖男性与健康男性其它血脂指标无明显差异。相关性分析显示TGAUC和TGPR分别与HOMA2-IR、腰围正相关。3.代谢综合征高危人群相关脂肪细胞因子的表达相关脂肪细胞因子水平：肥胖男性血清脂联素水平为3.15±2.18μg/ml，明显低于健康男性5.57±3.36μg/ml(P＜0.001)，瘦素水平明显高于健康男性(P＜0.001)。与健康男性相比，肥胖男性CRP、TNF-α及IL-6水平均明显升高(P＜0.01)，其PAI-1水平亦明显升高(P＜0.001)，t-PA水平则明显低于健康男性(P＜0.001)。相关性分析：脂联素分别与HOMA2-IR、腰围及体重指数呈负相关；瘦素与HOMA2-IR、腰围、体重指数正相关；CRP、IL-6、TNF-α与腰围正相关(P＜0.05)；PAI-1与腰围、HOMA2-IR正相关，t-PA与腰围呈负相关(P＜0.05)。腰围对各脂肪细胞因子都具有明显的影响意义。受试者脂肪餐后TGAUC及TGPR与脂联素、瘦素、CRP水平密切相关。多元逐步回归分析显示，瘦素、脂联素对TGAUC及TGPR最具有影响意义。4.散聚法对代谢综合征高危人群餐后脂代谢的作用及机制散聚法对代谢综合征高危人群餐后脂代谢的作用：治疗前后，中药组和安慰剂组空腹及脂肪餐后2小时TG浓度都无明显变化。治疗后中药组餐后第4小时TG浓度下降14.1％，但与治疗前相比无统计学差异，而安慰剂组TG浓度上升了15.6％，两治疗组间相比有统计学差异(P＜0.05)。治疗后，中药组脂肪餐后第6小时TG浓度下降28.3％，与治疗前相比有明显统计学差异(P＜0.05)，与安慰剂组相比，治疗前后变化有统计学差异(P＜0.05)。中药组第8小时TG浓度治疗后下降40.7％，与治疗前相比有显著性差异(P＜0.01)，与安慰剂组相比，治疗前后变化有明显差异(P＜0.05)。中药组治疗后TG各时相点浓度与正常对照组相比均无明显差异，且明显低于安慰剂组治疗后TG水平。治疗后，中药组TG峰值出现在第4小时，第8小时TG浓度与空腹水平已无明显差异。治疗后中药组与正常对照组脂肪餐后TG代谢趋势一致。治疗后，中药组TGAUC和TGPR明显下降(P＜0.01)，与安慰剂组相比治疗前后TGAUC和TGPR变化具有统计学意义(P＜0.05)。中药组治疗后TGAUC及TGPR与正常对照组相比已无明显差异，而与安慰剂组治疗后TGAUC及TGPR相比有明显差异(P＜0.01)。治疗前，中药组、安慰剂组空腹及餐后2、4、6、8小时血FFA浓度水平接近。治疗后，中药组空腹及餐后2、4小时FFA浓度下降明显(P＜0.01)，第6、8小时FFA浓度亦有明显下降(P＜0.05)，与安慰剂组相比均具有统计学差异(P＜0.05)。治疗后中药组各点FFA浓度与正常对照组相比无统计学差异。治疗后，中药组第8小时与第6小时FFA浓度相比有明显下降(P＜0.05)，与正常对照组代谢趋势一致。散聚法对代谢综合征高危人群餐后血糖及胰岛素代谢的作用：中药组和安慰剂组治疗前后空腹血糖及第2、4、6小时血糖均无明显变化，两组间相比无统计学差异。治疗后，中药组餐后2小时血糖明显高于正常对照组(P＜0.05)，其它各点血糖水平与正常对照组无明显差异。安慰剂组治疗后空腹血糖明显高于正常对照组(P＜0.05)，其它各点血糖水平与正常对照组及中药组无明显差异。治疗后，中药组空腹胰岛素水平明显下降(P＜0.01)，安慰剂组治疗前后空腹胰岛素水平无明显变化，两组间相比治疗前后变化存在显著性差异(P＜0.01)。中药组及安慰剂组治疗后餐后2、4、6、8小时胰岛素水平与治疗前相比均无明显变化。散聚法对代谢综合征高危人群一般状况的影响：治疗后，中药组体重指数、腰围、腰臀比及HOMA2-IR评分明显下降，治疗前后有明显差异(P＜0.001)，与安慰剂组相比具有统计学意义(P＜0.001)。中药组治疗后腰围、腰臀比均低于安慰剂组治疗后水平(P＜0.05)，HOMA2-IR评分则显著低于安慰剂组治疗后水平(P＜0.01)，且与正常对照组相比无明显差异。两组治疗前后收缩压及舒张压无明显改变。治疗后，中药组TC及LDL-c水平较治疗前明显下降(P＜0.01)，与安慰剂组相比治疗前后变化具有显著性差异(P＜0.01)。散聚法对代谢综合征高危人群相关脂肪细胞因子表达的影响：中药组肥胖患者体内脂联素水平治疗后有明显提高(P＜0.01)，与安慰剂组相比治疗前后变化具有统计学差异(P＜0.01)。中药组肥胖患者体内瘦素水平治疗后下降了21.6％，改变明显(P＜0.01)，与安慰剂组相比有统计学意义(P＜0.05)。治后中药组CRP、IL-6和TNF-α水平分别下降了39.7％、25.4％和24.4％，下降明显，与安慰剂组相比治疗前后变化具有统计学差异(P＜0.01)。中药组治疗后PAI-1平均水平下降了18.1％(P＜0.05)，两组治疗前后PAI-1变化具有明显差异(P＜0.05)，而t-PA水平则较治疗前上升了48.5％，治疗前后改变明显(P＜0.001)。中药组各脂肪细胞因子治疗后水平与正常对照组相比无明显差异。散聚法对代谢综合征高危人群临床表现的作用：中药组常见症状的总有效率为68.8％，安慰剂组常见症状的总有效率为11.9％，二者相比有显著性差异(P＜0.001)。治疗后，中药组在形体肥胖这一临床症状上有效率为30％，略高于安慰剂组，但无统计学意义(P＞0.05)。中药组治疗后肢体困重及自汗症状得到明显改善，有效率为分别为78.9％、75％，均明显高于安慰剂组(P＜0.001)。中药组治疗后患者气短乏力及脘腹痞满均有明显的改善，有效率分别为82.4％和77.8％。与安慰剂组相比有明显差异(P＜0.01、P＜0.05)。治疗后中药组其它临床症状包括胸闷、头晕、肢体麻木、大便干结等较治疗前有所好转，部分患者舌、苔、脉象也有所改善。安慰剂组未见有明显上述变化。治疗前中药组和安慰剂组肥胖患者症状总分(含舌、苔、脉象计分)分别为5.67±2.05分、5.82±2.16分，无明显差异。治疗后中药组症状总分为2.23±1.12分，平均总分比治疗前下降了61.7％，与治疗前相比有显著性差异(P＜0.001)，与安慰剂组相比有统计学差异(P＜0.001)。结论1.代谢综合征高危人群脂肪细胞储存能量功能受损，餐后脂代谢异常，表现为脂肪餐后血甘油三酯浓度的升高、甘油三酯清除速度的减慢和血游离脂肪酸浓度的升高；餐后脂代谢紊乱可发生于较早阶段，可先于空腹血脂异常及糖调节受损的发生，并与胰岛素抵抗和肥胖密切相关。2.代谢综合征高危人群机体脂肪组织的内分泌功能紊乱，并伴有炎症和纤溶系统功能受损，体内相关脂肪细胞因子表达异常，表现为脂联素及t-PA水平下降，而瘦素、CRP、TNF-α、IL-6及PAI-1水平升高。3.上述脂肪细胞因子的异常表达与机体肥胖程度、胰岛素抵抗程度密切相关。脂联素、瘦素和CRP与餐后甘油三酯曲线下面积及甘油三酯峰反应密切相关，脂联素和瘦素的水平对餐后脂代谢具有重要的影响意义。4.代谢综合征高危人群临床证候呈现虚实夹杂之象，主要有体形肥胖、肢体困重、气短乏力、自汗和脘腹痞满等表现，微观辨证显示其存在有聚证气化障碍特点，体内郁热、湿浊、瘀血等邪气在正虚(气化不足)的基础上参与聚证的发生和发展。5.散聚法治疗可以逆转代谢综合征高危人群餐后脂代谢紊乱，降低餐后甘油三酯浓度，加快甘油三酯的清除并降低血游离脂肪酸的浓度；这一作用与散聚法改善肥胖患者的肥胖程度和胰岛素抵抗、纠正相关脂肪细胞因子的表达有关。6.散聚法可以推动气化功能，消散留驻病邪，改善代谢综合征高危人群的实验室指标，并且可以明显改善临床症状，从微观与宏观上体现了中医药的疗效，并验证了聚证学说的科学性和适用性，体现了中医的整体观念和“上工治未病”的思想。更多还原

【Abstract】 Objective1. To observe clinical manifestations of central obese men at high risk of metabolic syndrome and make the features of aggregation syndrome clear so as to further the standardization of aggregation syndrome differentiation and make point of the microcosmic syndrome differentiation by basing on the laboratory examinations.2. To investigate the lipid absorption in central obese men after fat load in orde to find the metabolism features of both triglycerides and free fatty acids and evaluate the energy storage function of adipocyte.3. To measure insulin resistance and levels of some adipocytokines in central obese men so as to evaluate inflammation and fibrolysis in their bodies and discuss the roles of vital-qi deficiency (weak functional activity of qi) and pathogens excess in the generation and development of aggregation syndrome.4. To observe the effects of aggregation-dissipating on postprandial lipids metabolism, measure insulin resistance, expressions of the above adipocytokines and clinical manifestations in central obese men and discuss its mechanisms so as to verify the theory of aggregation syndrome. Methods1. Features of clinical manifestations in metabolic syndrome high risk populationForty five central obese men whose waist was or more than 90 centimeters and insulin resistance index was no less than 1 were recruited at the out-patient department. Initial screening included a medical history, physical examination, routine blood tests, and a 75-g oral glucose tolerance test. Subjects who were with abnormal fasting blood glucose or lipids or with impaired glucose tolerance were excluded. Clinical manifestations were collected and analyzed.2. Features of postprandial lipids metabolism in metabolic syndrome high risk populationSubjects The above 45 central obese men received the test. And 30 non-obese healthy male volunteers whose waist circumferences were lower than 90 centimeter with insulin resistance index lower than 1 were recruited as the normal sample.Fat load test A fat-rich meal with 1100 kcal total energy was fed to the subjects after fasting overnight. Blood was drawn at fasting state and every two hours after fat load. The 8th hour was the endpoint of the test and the samples were collected to measure the levels of serum triglyceride (TG), free fatty acid (FFA), blood glucose and insulin.Common tests Height, weight, waist and hip circumferences, systolic and diastolic blood pressure were measured. Body mass index (BMI), waist-to-hip ratio (WHR) and insulin resistance index (HOMA2-IR) were calculated and their correlations with postprandial lipids metabolism were analyzed. Other lipids indexes including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c) and lipoprotein-a were also measured.3. Levels of some related adipocytokines in metabolic syndrome high risk populationMeasurement of some related adipocytokines Blood was drawn from the above central obese men and non-obese healthy male volunteers to measure the levels of serum adiponectin, leptin, C reaction protein (CRP), interleukin-6 (IL-6), tumor necrosis factorα(TNF-α), plasma plasminogen activator inhibitor-1 (PAl-1) and tissue plasminogen activator (t-PA) with enzyme linked immunosorbent assay (ELISA) method.Correlation analysis The correlations between the above adipocytokines and obesity/insulin resistance and their correlations with postprandial lipids metabolism were analyzed with simple and multiple linear regression analysis respectively.4. Effects of aggregation-dissipating on lipids metabolism in metabolic syndrome high risk population and its mechanismEffects of aggregation-dissipating on postprandial iipids metabolism in metabolic syndrome high risk population The above 45 central obese men were separated into two groups randomly to receive 10-weeks intervention with Chinese medicine Yiqi Sanju Formula or placebo. Their former life styles were remained unchanged during the treatment. Fat load test was conducted before and after the treatment. TG. FFA, blood glucose and insulin levels was compared respectively before and after treatment.Impacts of aggregation-dissipating on general conditions in metabolic syndrome high risk population Changes of waist and hip circumference, height, blood pressure and other lipids including TC, LDL-c, HDL-c, and lipoprotein-a in the two groups were observed before and after treatment. Obesity and insulin resistance were. compared before and after treatment, too.Impacts of aggregation-dissipating on levels of some related adipocytokines in metabolic syndrome high risk population Adipocytokines including adiponectin, leptin, CRP, TNF-α、IL-6, PAI-1 and t-PA were measured and compared before and after treatment in the two groups.Impacts of aggregation-dissipating on clinical manifestations in metabolic syndrome high risk population Scores of clinical manifestations were recorded and compared before and after treatment in the two groups.Results1. Features of clinical manifestations in metabolic syndrome high risk populationIn the 45 central obese men, the most frequent clinical manifestations were obesity, heaviness in the body, shortness of breath and lassitude, spontaneous perspiration, mass and fullness in epigastrium. Other clinical manifestations were dizziness, stuffiness, numbness in the body, poor appetite, foul breath or bitter taste in the mouth, dry or loose stool, yellow or red urine, insomnia and dreaminess and so on. Tongue bodies were normal, red, or pale and enlarged with tooth dent in the margins. Tongue coatings included thin and white coating, white greasy coating, yellow greasy coating, thick greasy coating, little coating and so on. Pulses were normal, wiry, wiry and rapid, slippery, thready and rapid, full and large, soft and thready, deep and so on. The frequency of obesity was significantly higher than those of shortness of breath and lassitude, spontaneous perspiration and mass and fullness in epigastrium, while the frequency of heaviness in the body was higher than those of spontaneous perspiration and mass and fullness in epigastrium. Shortness of breath and lassitude occurred more frequently than mass and fullness in epigastrium.2. Features of postprandial lipids metabolism in metabolic syndrome high risk populationFeatures of postprandial TG and FFA metabolism in metabolic syndrome high risk population There was no difference in fating TG level between central obese and healthy men. The level of TG elevated significantly in central obese men from the 2nd hour after fat load (P＜0.01). The peak of TG in healthy men appeared at the 4th hour, earlier than that of obese men. The level of TG at 8th hour was close to its fasting TG level in healthy men, but TG level at 8th hour was still higher than its fasting TG level (P＜0.001), which indicated the slow clearance of TG in obese men. Both TG area under the curve (TGAUC) and TG peak reaction (TGPR) in obese men were significantly higher than those of healthy men.Compared with healthy men, the concentrations of FFA at fasting state and 2nd, 6th and 8th hour after fat load elevated significantly in obese men(P＜0.05). There was no statistical difference in FFA level at 4th hour between obese and healthy men. In obese men, the level of FFA at 6th elevated significantly and was higher than that of 4th hour (P＜0.05), while there was no difference in the levels at 4th and 6th hour in healthy men. FFA level from 6th to 8th hour dropped significantly in healthy men, but did not changed much in obese men.Features of postprandial glucose and insulin metabolism in metabolic syndrome high risk population There was no difference in fasting concentration of blood glucose between obese and healthy men. Compared with healthy men, levels of blood glucose at 2nd and 4th hour elevated significantly in obese men (P＜0.01 and P＜0.05 respectively). Levels of blood glucose at 6th hour were similar in the two groups. Compared with healthy men, insulin concentrations at fasting state and 2nd hour after fat load were elevated significantly in obese men (P＜0.001). Levels of insulin at 4th, 6th and 8th hour were similar in the two groups. From 4th hour after fat load, insulin levels began to drop and at 8th hour the levels were close to the fasting levels both in obese and healthy men.General conditions in metabolic syndrome high risk population: Compared with healthy men, body mass index, waist circumference and waist-to-hip ratio in obese men increased significantly (P＜0.001 for all comparisons), andf HOMA2-IR elevated significantly, too (P＜0.001). Systolic blood pressure in obese men was 7 mmHg higher than that of healthy men (P＜0.05). And the other lipids were similar in the two groups. HOMA2-IR and waist circumference were positively correlated to TGAUC and TGPR.3. Levels of some related adipocytokines in metabolic syndrome high risk populationLevels of the related adipocytokines Level of serum adiponectin in obese men was significantly lower than that of healthy men (3.15±2.18μg/ml vs 5.57±3.36μg/ml and P＜0.001 ), while leptin level was higher in obese men (P＜0.001). Compared with healthy men, levels of CRP, TNF-α, IL-6 and PAI-1 in obese men elevated significantly (P＜0.01) and t-PA decreased significantly (P＜0.001).Correlation analysis Adiponectin was negatively correlated to HOMA2-IR, waist circumference and BMI respectively. Leptin was positively correlated to HOMA2-IR, waist circumference and BMI. CRP, IL-6 and TNF-αwere positively correlated to waist circumference (P＜0.05). PAI-1 was positively correlated to HOMA2-IR and waist circumference, while t-PA was negatively correlated to waist circumference (P＜0.05). TGAUC and TGPR were closely related to adiponectin, leptin and CRP and multiple linear regression analysis showed levels of leptin and adiponectin had greatese impacts on TGAUC and TGPR.4. Effects of aggregation-dissipating on postprandial lipid metabolism in metabolic syndrome high risk populationEffects of aggregation-dissipating on postprandial lipid metabolism in metabolic syndrome high risk population There were no differences in TG concentrations at fasting state and 2nd hour before and after treatment in the two groups. TG concentration at 4th hour in Chinese medicine group was decreased by 14.1%, while TG level in placebo group increased by 15.6%. Compared with placebo, the Chinese medicine decreased TG concentrations at 2nd, 4th, 6th and 8th hour significantly (P＜0.05). After treatment, levels of TG at the five phases in Chinese medicine group were similar with those of healthy controls, and significantly lower than those of placebo group after treatment. After treatment, TG peak appeared at 4th hour and TG level at 8th hour was close to the level at fasting state in Chinese medicine group.Compared with placebo, the Chinese medicine decreased TGAUC and TGPR significantly (P＜0.05). TGAUC and TGPR in Chinese medicine group after treatment were similar with those of normal controls, but lower than those of placebo group (P＜0.01).Before treatment, levels of FFA in the two groups at the five phases were similar. After treatment, FFA levels at fasting state and 2nd and 4th hour in Chinese medicine group were decreased significantly (P＜0.01), and levels at 6th and 8th hour dropped significantly, too (P＜0.05). Compared with placebo, the Chinese medicine decreased FFA levels at all the five phases significantly (P＜0.05) and levels of FFA after treatment in Chinese medicine were close to the levels in healthy controls. After treatment, FFA level at 8th hour decreased significantly (P＜0.05 vs level at 6th hour) in Chinese medicine group and the same decrease was seen in healthy controls.Effects of aggregation-dissipating on postprandial blood glucose and insulin in metabolic syndrome high risk population: There were no significant changes in blood glucose at fasting state and 2nd, 4th and 6th hour after fat load after treatment in Chinese medicine group. The level of blood glucose at 2nd hour after treatment in Chinese medicine group was higher than that of healthy controls (P＜0.05).Compared with placebo, the Chinese medicine decreased insulin level significantly at fasting state (P＜0.01 for both comparisons). Neither the Chinese medicine nor the placebo changed insulin levels significantly at the four phases after fat load.Impacts of aggregation-dissipating on general conditions in metabolic syndrome high risk population There were significant decreases in BMI, waist circumference, waist-to-hip ratio and HOMA2-IR after treatment with the Chinese medicine (P＜0.001). Compared with placebo, the Chinese medicine decreased the four indexes significantly (P＜0.001). After treatment waist circumference and WHR in Chinese medicine group were lower than those of placebo group (P＜0.05). HOMA2-IR in Chinese medicine group was significantly lower than that of placebo group after treatment (P＜0.01) and similar with the score in healthy controls. Compared with placebo group, TC and LDL-c were decreased significantly in Chinese medicine group after treatment (P＜0.01).Impacts of aggregation-dissipating on the related adipocytokines levels in metabolic syndrome high risk population In Chinese medicine group, there was a significant increase in adiponectin level after treatment (P＜0.01) and the change was significant compared with placebo group (P＜0.01). There was a 21.6% decrease in leptin level in Chinese medicine group after treatment (P＜0.01) and the change was significant compared with placebo group (P＜0.05). Compared with placebo, the Chinese medicine decreased the levels of CRP, IL-6, TNF-αand PAI-1 by 39.7%, 25.4%, 24.4% and 18.1% respectively (P＜0.01 for CRP, IL-6, TNF-αcomparisons, and P＜0.05 for PAI-1 comparison with placebo group), and increased t-PA level by 48.5% (P＜0.001). After treatment with Chinese medicine, levels of all the above adipocytokines were similar with healthy controls.Impacts of aggregation-dissipating on clinical manifestations in metabolic syndrome high risk population The total effective rate in Chinese medicine group was 68.8%, while it was 11.9% in placebo group (P＜0.001 for the comparison of the two groups). Compared with placebo group, the symptom heaviness in the body and spontaneous perspiration were alleviated with effective rates of 78.9% and 75% respectively (P＜0.001 compared with placebo group). Symptom shortness of breath and lassitude and mass and fullness in epigastrium were also improved after treatment with the Chinese medicine with the effective rate 82.4% and 77.8% respectively (P＜0.01 and P＜0.05 for comparisons with placebo group). The other clinical manifestations including stuffiness, dizziness, numbness, dry stool were alleviated accompanied with improvement of tongue and tongue coating and pulse. The total scores of clinical manifestations in Chinese medicine group and placebo group were 5.67±2.05 and 5.82±2.16 respectively. Compared with placebo, the Chinese medicine decreased the total score of clinical manifestations significantly by 61.7% (P＜0.001 for both comparisons). Conclusions1. The energy storage function of adipocyte was impaired and postprandial lipid metabolism was abnormal in metabolic syndrome high risk population, indicated by elevation of TG concentrations, slow clearance of TG and elevation of FFA levels at postprandial state after fat load. The lipid disturbance could exit at early stage in metabolic syndrome high risk population and might be earlier than the occurrence of impaired glucose tolerance or abnormalities of fasting lipids.2. In metabolic syndrome high risk population, dysfunction of adipose tissue as an endocrine organ with chronic inflammation and impaired fribolysis was indicated by the abnormal levels of the related adipocytokines. Levels of adiponectin and t-PA were decreased while leptin, CRP, IL-6, TNF-αand PAI-1 levels increased.3. The levels of the above adipocytokines were closely related to central obesity and insulin resistance. Adiponectin, leptin and CRP was strongly correlated to TG area under curve and TG peak reaction. Abnormal levels of adiponectin and leptin might be risk factors of postprandial lipids metabolism.4. The main clinical manifestations in metabolic syndrome high risk population were obesity, heaviness in the body, shortness of breath and lassitude, spontaneous perspiration, mass and fullness in epigastrium. These manifestations were consistent with macroscopic differentiation of aggregation syndrome and microcosmic syndrome differentiation showed functional activity of qi was disordered accompanied by aggregation of pathogenic factors such as stagnated heat, turbid damp and blood stasis.5. Aggregation-dissipating reversed the abnormalities of postprandial lipids metabolism in metabolic syndrome high risk population by decreasing TG and FFA concentrations and accelerating TG clearance. Aggregation-dissipating improved central obesity and insulin resistance and regulated levels of the above adipocytokines in metabolic syndrome high risk population, which might be the mechanism of its effect on lipid metabolism.6. Aggregation-dissipating promoted functional activity of qi, dissipated aggregation of pathogenic factors, improved laboratory examinations and alleviated clinical manifestations in metabolic syndrome high risk population, which implicated efficacy of traditional Chinese medicine, verified the theory of aggregation syndrome and embodied the concept of wholism and the thought that veteran doctor took preventive measures of diseases in traditional Chinese medicine.更多还原