低聚果糖对原发性高血压作用效果的实验及临床试验研究
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摘要
研究背景
原发性高血压(essential hypertension, EH)是人类心血管疾病发病率最高的疾病之一,也是心、脑血管病最重要的危险因素之一。研究表明,我国每年约有233万人因高血压导致心血管病而死亡,其中127万人为过早死亡,22万人因高血压前期所致。高血压已成为威胁我国居民健康的头号杀手。统计结果显示,我国人群的高血压、高血压前期与全因死亡率及心血管死亡率增加明显相关。特别是高血压前期人群的高血压及心血管事件风险明显高于正常人群,是高血压的后备军。因此,高血压的预防和治疗同等重要,我国高血压的流行病学现状迫切要求我们的高血压预防战略要前,即重视处于高血压前期、未达到高血压诊断标准的人群,对其实施干预,从而有效预防和延缓高血压及并发症的发生。
目前对于原发性高血压的治疗,包括药物治疗与非药物治疗两种方法。非药物治疗主要通过合理饮食与调整生活方式来实现。随着对原发性高血压发病机制及对这一疾病认识的不断深入,目前对原发性高血压非药物治疗的研究已成为心血管研究领域的新的“热点”。国外已有多项人群试验表明,生活方式的改变对血压控制有益。而对饮食改善血压的研究较少。
膳食纤维作为一类不能被人体消化酶分解的食物成分,包括可溶性和非可溶性两大类,具有促进肠道功能、预防肠癌的作用,能降低血糖、调节血脂、预防冠状动脉粥样硬化性心脏病等心血管疾病的发生,对心血管有一定保护作用。美国的高血压指南建议高血压患者应尽可能多选择DASH饮食(Dietary Approaches to Stop Hypertension),即强调日常多食用水果、蔬菜和全谷类食物的重要性,因为这些食物能为患者提供膳食纤维的丰富来源。益生元属于可溶性膳食纤维,除了具有膳食纤维的作用外,还能够促进肠道益生菌的生长和活性,促进机体健康。已有研究证实,益生元对肥胖和心血管疾病具有一定的预防和治疗作用。在多种现有的益生元中,低聚果糖(Oligofructose, OFS)的应用最为广泛,因其具有良好的安全性,已经被添加到牛奶、饼干等食品当中。
本课题拟通过动物实验以及前瞻性的随机对照临床试验,研究低聚果糖对血压的影响,并初步探讨其作用的机制。
动物实验部分,通过高果糖喂饲大鼠诱导建立高血压伴胰岛素抵抗模型,同时给予低聚果糖,观察低聚果糖对大鼠血压、血糖和血脂的影响,并验证低聚果糖作为膳食添加的营养成分的安全性和有效性。
在临床试验中,通过随机、对照和盲法设计,以高血压前期人群作为观察对象,分别给予低聚果糖或安慰剂对照,并进行饮食和生活方式指导,观察低聚果糖对高血压前期人群的血压(收缩压、舒张压)、低密度脂蛋白、高密度脂蛋白、甘油三酯、胆固醇等指标的影响,评价低聚果糖应用于高血压前期人群的安全性及有效性,为益生元在高血压前期的非药物治疗中的应用提供的准确、可靠的临床试验依据。
第一部分
低聚果糖对高糖膳食诱导高血压大鼠作用效果的实验研究
目的
验证高果糖膳食诱导建立高血压大鼠模型的可行性,观察低聚果糖对高血压大鼠的血压、血脂及血糖的影响,初步探讨其可能的作用机制。方法
体重为110-120g的SD雄性大鼠30只,按体重随机分为对照组(C组)、喂饲高果糖饲料的高果糖组(F组)和在高果糖饲料中添加10%低聚果糖的低聚果糖组(OFS组),每组10只,共12周,记录每周进食量和体重。12周末,禁食12小时,麻醉后行葡萄糖钳夹试验评价胰岛素敏感性,然后经内眦取血,分离血清,测定空腹血糖、血脂(TG、TC、LDL、HDL),放射免疫法测定血清胰岛素和内脂素水平,比色法测定抗氧化酶活性和氧化产物。剥离肾周及睾周脂肪组织垫,吸干水分后称重,计算内脏脂肪系数。留取脂肪组织测定内脂素表达。留取肾脏进行HE染色组织形态学检查。结果
F组和OFS组大鼠体重均显著低于C组(P<0.05),F组和OFS组体重无显著差异。F组收缩压较C组显著升高(P<0.01),OFS组与F组相比收缩压显著降低(P<0.01),但仍较C组显著升高(P<0.01)。
F组和OFS组血浆TG水平与C组相比显著升高(P<0.01),且OFS组血TG水平与F组相比显著降低(P<0.01)。LDL水平F组显著高于C组(P<0.01),OFS组显著高于C组(P<0.01),但显著低于F组(P<0.01)。
F组和OFS组血糖及胰岛素水平与C组无显著性差异,F组GIR较C组显著降低(P<0.01),OFS组较C组显著降低(P<0.01),但较F组显著升高(P<0.01)。F组SOD活性与C组和OFS组相比显著降低(P<0.01),而OFS组与C组相比SOD活性无显著性差异。
F组内脏脂肪系数显著高于C组,OFS组内脏脂肪系数显著低于F组(P<0.01),与C组相比差异无显著性(P>0.05)。
F组血浆内脂素水平较C组显著升高(P<0.01),OFS组血浆内脂素水平较C组显著升高(P<0.05),但较F组显著性降低(P<0.05)。各组内脏脂肪的内脂素水平比较,F组显著高于C组(P<0.01),OFS组显著低于C组(P<0.05),OFS组较F组显著降低(P<0.05)。F组和OFS组内脏脂肪Visfatin表达较C组显著升高,而OFS组内脏脂肪Visfatin的表达较F组显著降低。
结论
1、高果糖喂饲可以成功建立高血压伴胰岛素抵抗大鼠模型,且成模率高,死亡率低。
2、低聚果糖对高血压大鼠的饲料摄入和体重无明显影响。
3、低聚果糖在一定程度上能降低高血压大鼠的血压。
4、低聚果糖可能通过减少内脏脂肪聚积、抑制内脏脂肪炎性因子释放、改善胰岛素抵抗,提高抗氧化能力、减轻肾脏氧化损伤,发挥降血压作用。
5、低聚果糖对高血压大鼠的血脂有一定的调节作用。
第二部分
低聚果糖对高血压前期人群作用的前瞻性临床试验研究
目的
通过随机对照的前瞻性临床试验研究,评价低聚果糖对高血压前期人群的血压及血脂的有效性和安全性,探索益生元作为高血压前期的非药物治疗方法的临床应用价值。
方法
采用随机、双盲、安慰剂对照试验设计,共12周。筛选符合纳入标准的受试者140人随机分入试验组和对照组,每组各70人,分别口服低聚果糖和麦芽糊精,同时接受饮食和生活方式的自我管理教育,以达到生活方式的均一化。入组前4周及试验期间需服药抗高血压治疗者,受试者的依从性通过填写食物和生活方式追踪表监测。随访共3次：0周、6周、12周。其中0周和12周清晨空腹抽血。主要研究指标包括血压(收缩压、舒张压),次要研究指标包括低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、甘油三酯、胆固醇,BMI、体成分分析、腰臀比等。安全性通过观察生命体征的变化(晨起血压、晨起心率、晨起体温)和实验室检查(血常规、尿常规、血生化)评价。所有受试者均自愿参加并签署知情同意书。
结果
试验随机化分组成功,所有受试者干预前各基线指标均无显著性差异。试验过程中,所有受试者均未出现严重不良反应。第2次随访(第6周)时,对照组有3人脱落,OFS组有2人脱落；第3次随访(第12周)时,对照组有1人脱落,另有2人未抽血进行生化检查；OFS组有3人脱落,另有2人未行抽血及生化检查。
第2次随访时,OFS组收缩压和舒张压测量值均显著低于对照组(P<0.05)；第3次随访时,OFS组收缩压测量值显著低于对照组(P<0.001),舒张压测量值显著低于对照组(P<0.05)。C组收缩压较干预前有所下降,但差异无统计学意义(P>0.05),OFS组收缩压较干预前显著下降(P<0.001),且OFS收缩压下降与C组相比更显著(P<0.05)。干预后,C组舒张压较干预前相比无显著性差异(P>0.05),OFS组舒张压较干预前显著下降(P<0.05),舒张压变化值OFS组较C组更显著(P<0.05)。
OFS组第2次和第3次随访的腰围测量值均显著低于对照组(P<0.05)。OFS组体质指数第2次随访时低于对照组(P<0.05),第3次随访时显著低于对照组(P<0.01)。
OFS组血胆固醇(TC)水平较对照组显著降低(P<0.05),血甘油三酯(TG)较对照组显著降低(P<0.05),高密度脂蛋白(HDL)水平无显著性差异(P>0.05),低密度脂蛋白(LDL)显著降低(P<0.05)。
结论
1、低聚果糖食用安全,无不良反应,能够作为日常饮食的有益营养补充。
2、低聚果糖对高血压前期人群具有一定的降血压作用,且对收缩压和舒张压都有改善,以收缩压下降为主。
3、低聚果糖对高血压前期人群的血脂具有调节作用,能够降低血胆固醇和甘油三酯的水平,起到心血管保护作用。
4、低聚果糖能降低高血压前期人群的腰围和体质指数,对高血压的防治有益。
Background
Essential hypertension (EH) as one of the important risk factors resulting cardiovascular diseases has high morbidity in China nowadays. It has been suggested that in our country 2,330,000 people die of cardiovascular events caused by hypertension. Prehypertension is an American classification for where a person's blood pressure is elevated above normal but not to the level considered to be hypertension, which blood pressure was read with a systolic pressure from 120 to 139 mm Hg or a diastolic pressure from 80 to 89 mm Hg. As soon as people were considered as prehypertension, non-drug therapy should be started to prevent development of hypertension. EH and prehypertension both have significant correlations with increase of crude death rate and mortality rate of cardiovascular diseases in our country. According to the epidemiology of EH that so many people have no awareness of their elevated blood pressure, non-drug treatment should be initiated when they were in prehypertension period.
The therapy of EH include anti-hypertension drugs and non-drug treatment, which consists mainly of healthy dietary replacement and lifestyle change programme. Trials of lifestyle change programmes have shown worthwhile improvements in blood pressure. But the researches were rare on dietary treatment improving blood pressure. Dietary fiber is the indigestible portion of plant foods that is readily fermented in the colon into gases and physiologically active byproducts, which can improve body health. It can protect gut health and prevent colon cancer, decrease blood glucose and adjust lipid to lower morbidity of coronary heart diseases and protect caridiovascular system. American Hypertension Guideline suggests hypertension patients should choose Dietary Approaches to Stop Hypertension (DASH), which means they should have more fruits, vegetables and grain in daily dietary to increase dietary fiber intake. Prebiotics, as one kind of soluble dietary fiber, is a nondigestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health. Prebiotics were proved to be effective in obesity, diabetes and dyslipidemia. Oligofructose(OFS), one of the most popular prebiotics, was widely used in food industry as an ingredient for milk and biscuits, etc.
Part1
Effects of oligofructose on blood pressure and lipids in hypertension rat model induced by high-fructose dietary
Object:To prove the feasibility of hypertension rat modeling by means of high-fructose feeding. To observe the effects of oligofructose on blood pressure, blood lipids and blood glucose in hypertension rats by determining daily intake, weight, fat, blood glucose, blood lipids and insulin level.
Methods:Thirty male Sprague-Dawley rats, weighting 110-120g, were the randomly assigned three groups included 10 rats:control group (standard feed, C group), high fructose group (high fructose feed, F group) and oligofructose group (high fructose feed with 10% oligofructose, OFS group). Weekly body weight and daily food intake were measured for 12 weeks. At the end of feeding period, the rats were sacrificed by anesthetizing with sodium pentobarbital (7ml/100g of body weight i.p.) after 12h of food deprivation. Hyperinsulinemic euglycemic clamp technique was performed to evaluate insulin sensitivity. Blood was collected and stored at-80℃for analysis. Blood plasma was stored at-20℃for fasting blood glucose, blood lipid (TG, TC, LDL, HDL) determination by automatic biochemical analyzer; plasma insulin and visfatin determination by ELISA; antioxidant enzyme activity and oxidation products level by colorimetry. The abdominal adipose tissues (perirenal, epididymal) were carefully removed using scissors and weighed for visceral fat index accouting and visfatin expression determination. Samples of kidney were kept in 10% formalin for pathological histology study.
Results:Weight of rats in F group and OFS group were significant lower than in C group and the difference between these two groups were not statistically significant. Blood pressure increased in F group and OFS group, and BP in OFS group was lower than in F group(P<0.05). There were no difference of total feed intake, blood glucose and fasting insulin level. GIR in F and OFS group decreased significantly compared with C group, whereas GIR in OFS group was higher than in F group. Visceral fat index (VFI) of rats in F group and OFS group were significant higher than in C group and VFC of rats in OFS group was lower than in F group(P<0.01). Total triglyceride, total cholesterol and LDL in F group and OFS group were higher than in C group(P<0.05). TC and HDL had no significant difference in F group and OFS group. Plasma visfatin in F group was higher than in C group and OFS group. Visceral visfatin in F group was highest and in OFS group was higher in three groups. Visfatin was highly expression in F group and OFS group, but expression in OFS group was lower than in F group.
Conclusion:
1. High-fructose feeding can successfully construct hypertension rat model, which was characterized with increased blood pressure and insulin resistance. This modeling method was efficient with low death rate.
2. Oligofructose has no significant effect on food intake and body weight.
3. Oligofructose can improve blood pressure in hypertension rats.
4. Oligofructose can decrease visceral fat accumulating and inflammatory factor level, which may improves insulin sensitivity in hypertension rats. It has effect on kidney protection which may acts by enhancing antioxidant capacity.
5. Oligofructose is beneficial to blood lipid in hypertension rats.
Part 2
Effects of oligofructose supplementation on blood pressure and lipid metabolism in prehypertensive people:a randomized, controlled prospective trial
Object:To observe the effect of oligofructose(OFS) supplementation on blood pressure and lipid metabolism in prehypertensive subjects.
Methods:A randomized, double-blinded, placebo-controlled trial was designed in the present study. A total of 140 adults aged 20 to 70 years with prehypertension were recruited from the community in Shanghai. All the participants signed the informed consents. Subject received anti-hypertension drugs were also excluded because of the interference of medication effect on blood pressure. All the participants were randomly assigned by using computer-generated random numbers to either receive 20g OFS per day (OFS group, n=70) or receive maltodextrin (control group, n=70) in a blinded fashion for 12 weeks. During the period a manual based self-management programme was developed for all participants in order to homogenize the lifestyle. Compliance was monitored using serial contemporaneous food and lifestyle trackers. The participants were interviewed at 0 w,6 w,12 w during the trial. Blood samples were collected at 0 w and 12 w. Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded as primary study outcomes. Secondary outcomes including blood total cholesterol, triglyceride and anthropometric data werecollected before and at the end of the treatment period.
Results:
Randomization was successful and there were no significant differences between groups in any of the baseline measures. No severe adverse reaction presents during the study period. In the 6th wk,3 participants quited the trial in control group and 2 in OFS group. In the 12th wk,1 quited and 2 failed to blood tests in control group.3 quited and 2 failed to blood tests in OFS group.
The measured outcomes showed more beneficial changes in OFS group. At the end of intervention, SBP and DBP was significant lower in OFS group than in control group. The decrease value of SBP in OFS group was higher than in control group. Waist circumference and BMI in OFS group were lower than in control group during 2nd follow-up. Participants in OFS group also had significantly lowered blood total cholesterol, triglyceride and LDL in OFS group than in control group.
Conclusion:
1. Oligofructose is safe used as beneficial additional to usual diet.
2. Oligofructose supplementation leads to a significant reduction in blood pressure in prehypertension subjects.
3. Oligofructose can decrease blood cholesterol and triglyceride in prehypertension subjects, which may protect cardiovascular system.
4. Oligofructose decreases waist circumference and BMI which may benefit to hypertension prevent and treatment.
原发性高血压(essential hypertension, EH)是人类心血管疾病发病率最高的疾病之一,也是心、脑血管病最重要的危险因素之一。研究表明,我国每年约有233万人因高血压导致心血管病而死亡,其中127万人为过早死亡,22万人因高血压前期所致。高血压已成为威胁我国居民健康的头号杀手。统计结果显示,我国人群的高血压、高血压前期与全因死亡率及心血管死亡率增加明显相关。特别是高血压前期人群的高血压及心血管事件风险明显高于正常人群,是高血压的后备军。因此,高血压的预防和治疗同等重要,我国高血压的流行病学现状迫切要求我们的高血压预防战略要前,即重视处于高血压前期、未达到高血压诊断标准的人群,对其实施干预,从而有效预防和延缓高血压及并发症的发生。
目前对于原发性高血压的治疗,包括药物治疗与非药物治疗两种方法。非药物治疗主要通过合理饮食与调整生活方式来实现。随着对原发性高血压发病机制及对这一疾病认识的不断深入,目前对原发性高血压非药物治疗的研究已成为心血管研究领域的新的“热点”。国外已有多项人群试验表明,生活方式的改变对血压控制有益。而对饮食改善血压的研究较少。
膳食纤维作为一类不能被人体消化酶分解的食物成分,包括可溶性和非可溶性两大类,具有促进肠道功能、预防肠癌的作用,能降低血糖、调节血脂、预防冠状动脉粥样硬化性心脏病等心血管疾病的发生,对心血管有一定保护作用。美国的高血压指南建议高血压患者应尽可能多选择DASH饮食(Dietary Approaches to Stop Hypertension),即强调日常多食用水果、蔬菜和全谷类食物的重要性,因为这些食物能为患者提供膳食纤维的丰富来源。益生元属于可溶性膳食纤维,除了具有膳食纤维的作用外,还能够促进肠道益生菌的生长和活性,促进机体健康。已有研究证实,益生元对肥胖和心血管疾病具有一定的预防和治疗作用。在多种现有的益生元中,低聚果糖(Oligofructose, OFS)的应用最为广泛,因其具有良好的安全性,已经被添加到牛奶、饼干等食品当中。
本课题拟通过动物实验以及前瞻性的随机对照临床试验,研究低聚果糖对血压的影响,并初步探讨其作用的机制。
动物实验部分,通过高果糖喂饲大鼠诱导建立高血压伴胰岛素抵抗模型,同时给予低聚果糖,观察低聚果糖对大鼠血压、血糖和血脂的影响,并验证低聚果糖作为膳食添加的营养成分的安全性和有效性。
在临床试验中,通过随机、对照和盲法设计,以高血压前期人群作为观察对象,分别给予低聚果糖或安慰剂对照,并进行饮食和生活方式指导,观察低聚果糖对高血压前期人群的血压(收缩压、舒张压)、低密度脂蛋白、高密度脂蛋白、甘油三酯、胆固醇等指标的影响,评价低聚果糖应用于高血压前期人群的安全性及有效性,为益生元在高血压前期的非药物治疗中的应用提供的准确、可靠的临床试验依据。
第一部分
低聚果糖对高糖膳食诱导高血压大鼠作用效果的实验研究
目的
验证高果糖膳食诱导建立高血压大鼠模型的可行性,观察低聚果糖对高血压大鼠的血压、血脂及血糖的影响,初步探讨其可能的作用机制。方法
体重为110-120g的SD雄性大鼠30只,按体重随机分为对照组(C组)、喂饲高果糖饲料的高果糖组(F组)和在高果糖饲料中添加10%低聚果糖的低聚果糖组(OFS组),每组10只,共12周,记录每周进食量和体重。12周末,禁食12小时,麻醉后行葡萄糖钳夹试验评价胰岛素敏感性,然后经内眦取血,分离血清,测定空腹血糖、血脂(TG、TC、LDL、HDL),放射免疫法测定血清胰岛素和内脂素水平,比色法测定抗氧化酶活性和氧化产物。剥离肾周及睾周脂肪组织垫,吸干水分后称重,计算内脏脂肪系数。留取脂肪组织测定内脂素表达。留取肾脏进行HE染色组织形态学检查。结果
F组和OFS组大鼠体重均显著低于C组(P<0.05),F组和OFS组体重无显著差异。F组收缩压较C组显著升高(P<0.01),OFS组与F组相比收缩压显著降低(P<0.01),但仍较C组显著升高(P<0.01)。
F组和OFS组血浆TG水平与C组相比显著升高(P<0.01),且OFS组血TG水平与F组相比显著降低(P<0.01)。LDL水平F组显著高于C组(P<0.01),OFS组显著高于C组(P<0.01),但显著低于F组(P<0.01)。
F组和OFS组血糖及胰岛素水平与C组无显著性差异,F组GIR较C组显著降低(P<0.01),OFS组较C组显著降低(P<0.01),但较F组显著升高(P<0.01)。F组SOD活性与C组和OFS组相比显著降低(P<0.01),而OFS组与C组相比SOD活性无显著性差异。
F组内脏脂肪系数显著高于C组,OFS组内脏脂肪系数显著低于F组(P<0.01),与C组相比差异无显著性(P>0.05)。
F组血浆内脂素水平较C组显著升高(P<0.01),OFS组血浆内脂素水平较C组显著升高(P<0.05),但较F组显著性降低(P<0.05)。各组内脏脂肪的内脂素水平比较,F组显著高于C组(P<0.01),OFS组显著低于C组(P<0.05),OFS组较F组显著降低(P<0.05)。F组和OFS组内脏脂肪Visfatin表达较C组显著升高,而OFS组内脏脂肪Visfatin的表达较F组显著降低。
结论
1、高果糖喂饲可以成功建立高血压伴胰岛素抵抗大鼠模型,且成模率高,死亡率低。
2、低聚果糖对高血压大鼠的饲料摄入和体重无明显影响。
3、低聚果糖在一定程度上能降低高血压大鼠的血压。
4、低聚果糖可能通过减少内脏脂肪聚积、抑制内脏脂肪炎性因子释放、改善胰岛素抵抗,提高抗氧化能力、减轻肾脏氧化损伤,发挥降血压作用。
5、低聚果糖对高血压大鼠的血脂有一定的调节作用。
第二部分
低聚果糖对高血压前期人群作用的前瞻性临床试验研究
目的
通过随机对照的前瞻性临床试验研究,评价低聚果糖对高血压前期人群的血压及血脂的有效性和安全性,探索益生元作为高血压前期的非药物治疗方法的临床应用价值。
方法
采用随机、双盲、安慰剂对照试验设计,共12周。筛选符合纳入标准的受试者140人随机分入试验组和对照组,每组各70人,分别口服低聚果糖和麦芽糊精,同时接受饮食和生活方式的自我管理教育,以达到生活方式的均一化。入组前4周及试验期间需服药抗高血压治疗者,受试者的依从性通过填写食物和生活方式追踪表监测。随访共3次：0周、6周、12周。其中0周和12周清晨空腹抽血。主要研究指标包括血压(收缩压、舒张压),次要研究指标包括低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、甘油三酯、胆固醇,BMI、体成分分析、腰臀比等。安全性通过观察生命体征的变化(晨起血压、晨起心率、晨起体温)和实验室检查(血常规、尿常规、血生化)评价。所有受试者均自愿参加并签署知情同意书。
结果
试验随机化分组成功,所有受试者干预前各基线指标均无显著性差异。试验过程中,所有受试者均未出现严重不良反应。第2次随访(第6周)时,对照组有3人脱落,OFS组有2人脱落；第3次随访(第12周)时,对照组有1人脱落,另有2人未抽血进行生化检查；OFS组有3人脱落,另有2人未行抽血及生化检查。
第2次随访时,OFS组收缩压和舒张压测量值均显著低于对照组(P<0.05)；第3次随访时,OFS组收缩压测量值显著低于对照组(P<0.001),舒张压测量值显著低于对照组(P<0.05)。C组收缩压较干预前有所下降,但差异无统计学意义(P>0.05),OFS组收缩压较干预前显著下降(P<0.001),且OFS收缩压下降与C组相比更显著(P<0.05)。干预后,C组舒张压较干预前相比无显著性差异(P>0.05),OFS组舒张压较干预前显著下降(P<0.05),舒张压变化值OFS组较C组更显著(P<0.05)。
OFS组第2次和第3次随访的腰围测量值均显著低于对照组(P<0.05)。OFS组体质指数第2次随访时低于对照组(P<0.05),第3次随访时显著低于对照组(P<0.01)。
OFS组血胆固醇(TC)水平较对照组显著降低(P<0.05),血甘油三酯(TG)较对照组显著降低(P<0.05),高密度脂蛋白(HDL)水平无显著性差异(P>0.05),低密度脂蛋白(LDL)显著降低(P<0.05)。
结论
1、低聚果糖食用安全,无不良反应,能够作为日常饮食的有益营养补充。
2、低聚果糖对高血压前期人群具有一定的降血压作用,且对收缩压和舒张压都有改善,以收缩压下降为主。
3、低聚果糖对高血压前期人群的血脂具有调节作用,能够降低血胆固醇和甘油三酯的水平,起到心血管保护作用。
4、低聚果糖能降低高血压前期人群的腰围和体质指数,对高血压的防治有益。
Background
Essential hypertension (EH) as one of the important risk factors resulting cardiovascular diseases has high morbidity in China nowadays. It has been suggested that in our country 2,330,000 people die of cardiovascular events caused by hypertension. Prehypertension is an American classification for where a person's blood pressure is elevated above normal but not to the level considered to be hypertension, which blood pressure was read with a systolic pressure from 120 to 139 mm Hg or a diastolic pressure from 80 to 89 mm Hg. As soon as people were considered as prehypertension, non-drug therapy should be started to prevent development of hypertension. EH and prehypertension both have significant correlations with increase of crude death rate and mortality rate of cardiovascular diseases in our country. According to the epidemiology of EH that so many people have no awareness of their elevated blood pressure, non-drug treatment should be initiated when they were in prehypertension period.
The therapy of EH include anti-hypertension drugs and non-drug treatment, which consists mainly of healthy dietary replacement and lifestyle change programme. Trials of lifestyle change programmes have shown worthwhile improvements in blood pressure. But the researches were rare on dietary treatment improving blood pressure. Dietary fiber is the indigestible portion of plant foods that is readily fermented in the colon into gases and physiologically active byproducts, which can improve body health. It can protect gut health and prevent colon cancer, decrease blood glucose and adjust lipid to lower morbidity of coronary heart diseases and protect caridiovascular system. American Hypertension Guideline suggests hypertension patients should choose Dietary Approaches to Stop Hypertension (DASH), which means they should have more fruits, vegetables and grain in daily dietary to increase dietary fiber intake. Prebiotics, as one kind of soluble dietary fiber, is a nondigestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health. Prebiotics were proved to be effective in obesity, diabetes and dyslipidemia. Oligofructose(OFS), one of the most popular prebiotics, was widely used in food industry as an ingredient for milk and biscuits, etc.
Part1
Effects of oligofructose on blood pressure and lipids in hypertension rat model induced by high-fructose dietary
Object:To prove the feasibility of hypertension rat modeling by means of high-fructose feeding. To observe the effects of oligofructose on blood pressure, blood lipids and blood glucose in hypertension rats by determining daily intake, weight, fat, blood glucose, blood lipids and insulin level.
Methods:Thirty male Sprague-Dawley rats, weighting 110-120g, were the randomly assigned three groups included 10 rats:control group (standard feed, C group), high fructose group (high fructose feed, F group) and oligofructose group (high fructose feed with 10% oligofructose, OFS group). Weekly body weight and daily food intake were measured for 12 weeks. At the end of feeding period, the rats were sacrificed by anesthetizing with sodium pentobarbital (7ml/100g of body weight i.p.) after 12h of food deprivation. Hyperinsulinemic euglycemic clamp technique was performed to evaluate insulin sensitivity. Blood was collected and stored at-80℃for analysis. Blood plasma was stored at-20℃for fasting blood glucose, blood lipid (TG, TC, LDL, HDL) determination by automatic biochemical analyzer; plasma insulin and visfatin determination by ELISA; antioxidant enzyme activity and oxidation products level by colorimetry. The abdominal adipose tissues (perirenal, epididymal) were carefully removed using scissors and weighed for visceral fat index accouting and visfatin expression determination. Samples of kidney were kept in 10% formalin for pathological histology study.
Results:Weight of rats in F group and OFS group were significant lower than in C group and the difference between these two groups were not statistically significant. Blood pressure increased in F group and OFS group, and BP in OFS group was lower than in F group(P<0.05). There were no difference of total feed intake, blood glucose and fasting insulin level. GIR in F and OFS group decreased significantly compared with C group, whereas GIR in OFS group was higher than in F group. Visceral fat index (VFI) of rats in F group and OFS group were significant higher than in C group and VFC of rats in OFS group was lower than in F group(P<0.01). Total triglyceride, total cholesterol and LDL in F group and OFS group were higher than in C group(P<0.05). TC and HDL had no significant difference in F group and OFS group. Plasma visfatin in F group was higher than in C group and OFS group. Visceral visfatin in F group was highest and in OFS group was higher in three groups. Visfatin was highly expression in F group and OFS group, but expression in OFS group was lower than in F group.
Conclusion:
1. High-fructose feeding can successfully construct hypertension rat model, which was characterized with increased blood pressure and insulin resistance. This modeling method was efficient with low death rate.
2. Oligofructose has no significant effect on food intake and body weight.
3. Oligofructose can improve blood pressure in hypertension rats.
4. Oligofructose can decrease visceral fat accumulating and inflammatory factor level, which may improves insulin sensitivity in hypertension rats. It has effect on kidney protection which may acts by enhancing antioxidant capacity.
5. Oligofructose is beneficial to blood lipid in hypertension rats.
Part 2
Effects of oligofructose supplementation on blood pressure and lipid metabolism in prehypertensive people:a randomized, controlled prospective trial
Object:To observe the effect of oligofructose(OFS) supplementation on blood pressure and lipid metabolism in prehypertensive subjects.
Methods:A randomized, double-blinded, placebo-controlled trial was designed in the present study. A total of 140 adults aged 20 to 70 years with prehypertension were recruited from the community in Shanghai. All the participants signed the informed consents. Subject received anti-hypertension drugs were also excluded because of the interference of medication effect on blood pressure. All the participants were randomly assigned by using computer-generated random numbers to either receive 20g OFS per day (OFS group, n=70) or receive maltodextrin (control group, n=70) in a blinded fashion for 12 weeks. During the period a manual based self-management programme was developed for all participants in order to homogenize the lifestyle. Compliance was monitored using serial contemporaneous food and lifestyle trackers. The participants were interviewed at 0 w,6 w,12 w during the trial. Blood samples were collected at 0 w and 12 w. Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded as primary study outcomes. Secondary outcomes including blood total cholesterol, triglyceride and anthropometric data werecollected before and at the end of the treatment period.
Results:
Randomization was successful and there were no significant differences between groups in any of the baseline measures. No severe adverse reaction presents during the study period. In the 6th wk,3 participants quited the trial in control group and 2 in OFS group. In the 12th wk,1 quited and 2 failed to blood tests in control group.3 quited and 2 failed to blood tests in OFS group.
The measured outcomes showed more beneficial changes in OFS group. At the end of intervention, SBP and DBP was significant lower in OFS group than in control group. The decrease value of SBP in OFS group was higher than in control group. Waist circumference and BMI in OFS group were lower than in control group during 2nd follow-up. Participants in OFS group also had significantly lowered blood total cholesterol, triglyceride and LDL in OFS group than in control group.
Conclusion:
1. Oligofructose is safe used as beneficial additional to usual diet.
2. Oligofructose supplementation leads to a significant reduction in blood pressure in prehypertension subjects.
3. Oligofructose can decrease blood cholesterol and triglyceride in prehypertension subjects, which may protect cardiovascular system.
4. Oligofructose decreases waist circumference and BMI which may benefit to hypertension prevent and treatment.
引文
[1]He J, Gu D, Chen J, et al. Premature deaths attributable to blood pressure in China:a prospective cohort study[J]. Lancet.2009; 374(9703):1765-1772.
[2]Wang L, Kong L, Wu F, et al. Preventing chronic diseases in China[J]. Lancet.2005; 366(9499):1821-1824.
[3]Kiely AE, Kwatra SG, Kwatra MM. Treating prehypertension:medically sound and economically viable[J]. Blood Press.2009; 18(6):300-303.
[4]Whitworth JA; World Health Organization, International Society of Hypertension Writing Group.2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension[J]. J Hypertens.2003; 21(11):1983-1992.
[5]中国高血压防治指南(修订版).中华人民共和国卫生部.2005.
[6]Kokubo Y, Kamide K. High-normal blood pressure and the risk of cardiovascular disease[J]. Circ J.2009; 73(8):1381-1385.
[7]Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure[J]. Hypertension.2003; 42(6):1206-1252.
[8]Gibson GR, Roberfroid MB. Dietary modulation of the colonic microbiota:Introducing the concept of prebiotics. J Nutr.1995;125:1401-1412.
[9]Roberfroid MB. Prebiotics and probiotics:are they functional foods?[J]. Am J Clin Nutr. 2000; 71(6):1682S-1687S.
[10]Roberfroid MB. Functional foods:concepts and application to inulin and Oligofructose. Br J Nutr.2002; 87(Suppl 2):S139-143.
[11]Kathy R Niness. Inulin and Oligofructose:What Are They?[J]. J Nutr.1999; 129: 1402S-1406S.
[12]Marcel B Roberfroid. Inulin-Type Fructans:Functional Food Ingredients[J]. J Nutr.2007; 137(11):2493S-2502S.
[13]Solymoss B C, Marcil M, Chaour M, et al. Fasting hyperinsulinism, insulin resistance syndrome, and coronary artery disease in men and women[J]. Am J Cardliol.1995; 76: 1152-1156.
[14]De Fronzo RA, Ferrannini E. A multifaced syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia and atherosclerotic cardiovascular disease[J]. Diabetes Care.
1991; 14:173-194.
[15]Reaven G M, Ho H. Sugar induced hypertension in Sprague Dawley rats[J]. Am J Hypertens, 1991,4:610-614.
[16]陈川,胡英华.胰岛素与高血压的关系[J].中华内科杂志,1992;31：354.
[17]Denker P S, Pollock V E. Fasting serum insulin levels in essential hypertension-A meta-analysis[J]. Arch Intern Med.1992; 152:1649-1651.
[18]Possemiers S, Grootaert C, Vermeiren J, et al. The intestinal environment in health and disease-recent insights on the potential of intestinal bacteria to influence human health[J]. Curr Pharm Des.2009; 15(18):2051-2065.
[19]S. Kolida, K. Tuohy, G. R. Gibson, Prebiotic effects of inulin and oligofructose[J]. Br J Nutr. 2002; 87(S2):S193-S 197.
[20]Catena C, Giacchetti G, Novello M, et al. Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension[J]. Am J Hypertens.2003; 16(11):973-978.
[21]Falkner B, Hulman S, Tannenbaum J, et al. Insulin resistance and blood pressure in young black men[J]. Hypertension.1990; 16(6):706-711.
[22]Brands M W, Hall J E, Keen H L. Is insulin resistance linked to hypenension?[J]. Clinical and Experimental and Phamacology and Physiology,1998,25(1):70-76.
[23]Taek C J, Smits P, Willemsen J, et al. Effects of insulin on vascular tone and sympathetic nervous system in NIDDM[J]. Diabetes.1996; 45(1):15-22.
[24]Zemel M B. Insulin resistance vs. hyperinsulinemia in hypertension:insulin regulation of Ca2+ transport and Ca2+ -regulation of insulin sensitivity[J]. J Nutr.1995; 125:1738-1743.
[25]Slater E. Insulin resistance and hypertension[J]. Hypertension.1991; 18(3):S1108-1114.
[26]Zemel M B, Bedford B A, Zemel P C, et al. Altered cation transport in non-insulin-dependent diabetic hypertension:effects of dietary calcium[J]. J Hypertens.1988,6(4):S228-230.
[27]Nagai M, Kamide K, Rakugi H, et al. Role of endothelin-1 induced by insulin in the regulation of vascular cell growth[J]. Am J Hypertens,2003,16:223-228.
[28]Dhalla NS, Temsah RM, Netticadan T. Role of oxidative stress in cardiovascular diseases[J]. J Hypertens,2000,18:655-673.
[29]Frank H J, Levin E R, Hu R M. et al. Insulin stimulates endothelin binding and action on cultured vascular smooth muscle cells[J]. Endocrinology.1993; 133(3):1092.
[30]陈颜芳,韩启德.胰岛素抵抗大鼠血.压升高的血管机制[J].中国病理生理杂志.1998;14(5)：458-461.
[31]Axelrod L. Insulin, prostaglandins, and the pathogenesis of hypertension[J]. Diabetes.1991; 10:1223-1227.
[32]Zarjevski N, Cusin I, Vettor R, et al. Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity[J]. Endocrinology.1993,133(4):1753-1758.
[33]Han JR, Deng B, Sun J. Effects of dietary medium-chain triglyceride on weight loss and
insulin sensitivity in a group of moderately overweight free-living type 2 diabetic Chinese subjects [J]. Metabolism.2007,56(7):985-991.
[34]王绍云,宋怀东,李荣英.高脂大鼠抵抗素基因的上调表达及与胰岛素、瘦素的相关性[J].中华内分泌代谢杂志,2003,19(3).
[35]DeFronzo RA. Dysfunctional fat cells, lipotoxicity and type 2 diabetes[J]. Int J Chn Pract, 2004; 143(Suppl):9-21.
[36]Heilbronn L, Smith SR, Ravussin E. Failure of fat cell proliferation, mitochondrial function and fat oxidation results in ectopic fat storage, insulin resistance and type 2 diabetes melitus[J]. Int J Obes Relat Metab Disord,2004; 28(Suppl 4):S12-21.
[37]Fukuhara A, Matsuda M, Nishizawa M, et al. Visfatin:a protein secreted by visceral fat that mimics the effects of insulin[J]. Science.2005; 307(5708):426-430.
[38]Chen MP, ChungFM, Chang DM, et al. Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus[J]. J Clin Endocrinol Metab, 2006; 91(1):295-299.
[39]Ognjanovic S, Bryant Greenwood GD. Pre-B-cell colony-enhancing factor, a novel cytokine of human fetal membranes[J]. Am J Obstet Gynecol.2002; 187(4):1051-1058.
[40]Delzenne NM, Daubioul C, Neyrinck M, et al. Inulin and oligofructose modulate lipid metabolism in animals:review of biochemical events and future prospects[J]. Br J Nutr. 2002;87:S255-259.
[41]Kok N, Morgan L, Williams C, et al. Insulin, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide and insulin-like growth factor I as putative mediators of the hypolipidemic effect of oligofructose in rats[J]. J Nutr.1998; 128:1099-1103.
[42]Daubioul C, De Wispelaere L, Taper H, et al. Dietary oligofructose lessens hepatic steatosis, but does not prevent hypertriglyceridemia in obese Zucker rats[J]. J Nutr.2000; 130:1314-1319.
[43]Oku T, Tokunaga T, Hosoya N. Non digestibility of a new sweetener "Neosugar" in the rat[J]. J Nutr.1984; 114:1574-81.
[44]Gibson G, Roberfroid M, Colonic microbiota, nutrition and health[M]. The Netherlands: Kluwer Academic Publishers,1999:55-70.
[45]Delzenne NM, Daubioul C, Neyrinck M, et al. Inulin and oligofructose modulate lipid metabolism in animals:review of biochemical events and future prospects[J]. Br J Nutr.2002; 87:S255-259.
[46]Delzenne N, Kok N, Deloyer P, et al. Polyamines as mediators of physiological effects of dietary oligofructose in rats[J]. J Nutr.2000; 130:2456-2460.
[47]Drucker DJ. Biological actions and therapeutic potential of the glucagons-like peptides[J]. Gastroenterology.2002; 122:531-544.
[48]Sakata I, Nakamura K, Yamazaki M, et al. Ghrelin-producing cells exist as two types of cells, closed-and opened-type cells, in the rat gastrointestinal tract[J]. Peptides.2002; 23:531-536.
[1]张璐,孔灵芝,预防慢性病：一项至关重要的投资——世界卫生组织报告[J].中国慢性病预防与控制.2006;14(1)：1-4.
[2]He J, Gu D, Chen J, et al. Premature deaths attributable to blood pressure in China:a prospective cohort study[J]. Lancet.2009; 374(9703):1765-1772.
[3]Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure[J]. Hypertension.2003; 42(6):1206-1252.
[4]Wang L, Kong L, Wu F, et al. Preventing chronic diseases in China[J]. Lancet.2005; 366(9499):1821-1824.
[5]Stevens VJ, Obarzanek E, Cook NR, et al. Long-term weight loss and changes in blood pressure:results of the Trials of Hypertension Prevention, Phase Ⅱ[J]. Ann Intern Med.2000; 134:1-11.
[6]Kiely AE, Kwatra SG, Kwatra MM. Treating prehypertension:medically sound and economically viable[J]. Blood Press.2009; 18(6):300-303.
[7]中国高血压防治指南(修订版).中华人民共和国卫生部.2005.
[8]Whitworth JA; World Health Organization, International Society of Hypertension Writing Group.2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension[J]. J Hypertens.2003; 21(11):1983-1992.
[9]Appel L J, Moore T J, Obarzanek E, etal, A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group[J]. N Engl J Med.1997, 336(16):1117-24.
[10]Appel LJ, Champagne CM, Harsha DW, Effects of comprehensive lifestyle modification on blood pressure control:main results of the PREMIER clinical trial[J]. JAMA.2003; 289(16):2083-2093.
[11]Burke V, A lifestyle programme for treated hypertensive improved health-related behaviours and cardiovascular risk factors, a randomized controlled trial[J]. Journal of Clinical Epidemiology.2007,60:133-141.
[12]Gibson GR, Roberfroid MB. Dietary modulation of the colonic microbiota:Introducing the concept of prebiotics[J]. J Nutr.1995; 125(6):1401-1412.
[13]Marcel B Roberfroid. Inulin-Type Fructans:Functional Food Ingredients[J]. J Nutr.2007;
137(11):2493S-2502S.
[14]Roberfroid MB. Functional foods:concepts and application to inulin and Oligofructose[J]. Br J Nutr.2002; 87(Suppl 2):S139-143.
[15]Rault-Nania MH, Demougeot C, Gueux E, et al. Inulin supplementation prevents high fructose diet-induced hypertension in rats[J]. Clin Nutr.2008; 27(2):276-282.
[16]Busserolles J, Gueux E, Rock E, Oligofructose protects against the hypertriglyceridemic and pro-oxidative effects of a high fructose diet in rats[J]. J Nutr.2003; 133(6):1903-1908.
[17]The Seventh Report of the Joint National Committee on High Blood Pressure (JNC-7),2003.
[18]O'Brien E. Blood pressure measurement:recommendations of the British Hypertension Society 3rd edition[M]. London:BMJ Publishing Group; 1997.
[19]Amorim PR, de Faria RC, Byrne NM, et al. Physical activity and nutritional status of children of low socioeconomic status. Two interrelated problems:undernutrition and overweight[J]. Asia Pacific Journal of Clinical Nutrition.2006; 15:2172-23.
[20]Qu NN, Li KJ. Study on reliability and validity of the IPAQ Chinese version[J]. Chinese Journal of Epidemiology.2004; 25(3):265-268.
[21]Shu XO, et al. Validity and reproducibility of the food frequency questionnaire used in the Shanghai Women's Health Study[J]. European Journal of Clinical Nutrition.2004; 58:17-23.
[22]Ware J, Kosinski M, Keller S. A 12-item short-form health survey:Construction of scales and preliminary tests of reliability and validity[J]. Medical Care.1996; 34(3):220-233.
[23]Lin JD, et al.24 h ambulatory blood pressure among 200 middle-aged and old people[J]. Chinese Journal of Cardiovascular Rehabilitation Medicine 2000,9(2):24-26.
[24]Guidelines on Prevention and Treatment of Hypertension in China.
[25]Appel LJ, et al.:A clinical trial of the effects of dietary patterns on blood pressure[J]. N Engl J Med.1997,336:1117-24.
[26]Trials of Hypertension Collaborative Research Group:Effects of weight loss and sodium reduction intervention on blood pressure incidence in overweight people with high-normal blood pressure:the trials of hypertension prevention (phase 2) [J]. Arch Intern Med 1997, 157:657-667.
[27]Kelley G, McClellan P. Antihypertensive effects of aerobic exercise. A brief meta-analytic review of randomized controlled trials[J]. Am J Hypertens.1994; 7(2):115-119.
[28]Kokubo Y, Kamide K. High-normal blood pressure and the risk of cardiovascular disease. Circ J.2009; 73(8):1381-1385.
[29]Germino FW. JNC 8:expectations, challenges, and wishes-a primary care perspective[J]. J Clin Hypertens (Greenwich).2009; 11(10):573-576.
[1]Gibson. G. R. Invitro and In vivo effects of oligofructose and Inulin on the colonic microbiota, in ORAFTI 1st ORAFTI Research conference proceedings 1995(Brussels)
[2]熊德鑫,近代微生态学,北京：中国科技出版社,2000.
[3]郭兴华,益生菌,北京：北京科技出版社.2002.
[4]Hidaka. H, Effects of Fructooligo saeeharides on Intestinal Flora[J], Bifidobacteria Microflora,1986:5(1)37-50
[5]Beghin Meigi, "Actilighf"Introduction the world's first health ingredient 2002
[6]张田珍,木寡糖特性和生理功能[J],食品工业月刊,2001：33(6)12
[7]罔田茂寿等,工业用糖质酵素Handbook,东京：相谈社Scientific,1999,113-146
[8]Yoji Iikura, Food Allergy and Liver Function——preventive Effects of Drugs and Directory Fructoligo saccharides[J]. Bioscience Microflora.2002:21(1)69-72
[9]Yamashita. K, Effects of Fructooligosaccharides on blood glucose and serum lipids In Diabetic subjects[J], Nutr Research,1984:(4) 961
[10]Ham. Y, Studies on Relationship between Intake of FOS and Abdominal symptoms [J], Geriatric Medicine,1985:23(5)817-828
[11]Ohm. A, Effect of FOS and other saccharides on Ca, Mg and P absorption in rate[J], Jap Soc Nutr Food Sci,46,123-129
[1]张璐,孔灵芝,预防慢性病：一项至关重要的投资——世界卫生组织报告[J].中国慢性病预防与控制.2006;14(1):1-4.
[2]于修成.循证医学与医疗卫生决策[J].中国循证医学.2001;1:1-2.
[3]2003 World Health Organization(WHO)/International Society of Hypertension(ISH) statement on management of hypertension[J]. J Hypertens,2003,21(11):1983-1992.
[4]Paulk, Whehon MD, Lawrence A, et al. The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels. Results of the trials of hypertension prevention, phase I[J]. JAMA.1992; 267:1213-1220.
[5]Stevens VJ, Obarzanek E, Cook NR, et al. Long-term weight loss and changes in blood pressure:results of the Trials of Hypertension Prevention, Phase II[J]. Ann Intern Med.2000; 134: 1-11.
[6]Paulk. Whehon, Lawrence J, et al. Sodium reduction and weight loss in the treatment of hypertension in older persons[J]. JAMA.1998; 279:839-846.
[7]The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Presure[J]. JAMA.2003; 289:2560-2572.
[8]Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood presure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet[J]. N Engl J Med.2001; 344:3-10.
[9]Miller ER, Erlinger TP, Young DR, et al. Results of the Diet, Exercise and Weight Loss Intervention Trial (DEW-IT)[J]. Hypertension.2002; 40:612-618.
[10]Edgar R. Miller, Thomas P. Ertinger, et al. Writing Group of the PREMIER Colaborative Research Group. Effects of comprehensive lifestyle modification on blood pressure control:main results of the PREMIER clinical trial[J]. JAMA.2003; 289:2083-2093.
[11]Herbert G. Langford, Barry R. Davis, Donald B laufox, et al. Effect of drug and diet treatment of mild hypertension on diastolic blood pressure[J]. Hypertension.1991; 17:210-217.
[12]Sylvia wassertheil Smoller, M. Donald Blaufox, Albert Oberman, et al. The trial of antihypertensive interventions and management(TAIM) study[J]. Arch Intern Med.1992; 152: 131-136.
[13]Sylvia wasseaheil smoller, Donald Blaufox, Albert Oberman, et al. Effect of antihypertensives on sexual function and quality of life:the TAIM study[J]. Ann Intern Med,1991; 114:613-620.
[14]Victor J. Stevens, Eva Obarzanek, Manly R. Sid, et al. Long term weight loss and changes in blood pressure:results of the trials of hypertension prevention, phase II [J]. Ann Intern Med.2001; 134:1-11.
[15]Brand M, Mulrow C, Lom J, et al. Nonpharmaeological therapy of Hypertension on elderly[C]. Cochrane Library.2000.
[2]Wang L, Kong L, Wu F, et al. Preventing chronic diseases in China[J]. Lancet.2005; 366(9499):1821-1824.
[3]Kiely AE, Kwatra SG, Kwatra MM. Treating prehypertension:medically sound and economically viable[J]. Blood Press.2009; 18(6):300-303.
[4]Whitworth JA; World Health Organization, International Society of Hypertension Writing Group.2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension[J]. J Hypertens.2003; 21(11):1983-1992.
[5]中国高血压防治指南(修订版).中华人民共和国卫生部.2005.
[6]Kokubo Y, Kamide K. High-normal blood pressure and the risk of cardiovascular disease[J]. Circ J.2009; 73(8):1381-1385.
[7]Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure[J]. Hypertension.2003; 42(6):1206-1252.
[8]Gibson GR, Roberfroid MB. Dietary modulation of the colonic microbiota:Introducing the concept of prebiotics. J Nutr.1995;125:1401-1412.
[9]Roberfroid MB. Prebiotics and probiotics:are they functional foods?[J]. Am J Clin Nutr. 2000; 71(6):1682S-1687S.
[10]Roberfroid MB. Functional foods:concepts and application to inulin and Oligofructose. Br J Nutr.2002; 87(Suppl 2):S139-143.
[11]Kathy R Niness. Inulin and Oligofructose:What Are They?[J]. J Nutr.1999; 129: 1402S-1406S.
[12]Marcel B Roberfroid. Inulin-Type Fructans:Functional Food Ingredients[J]. J Nutr.2007; 137(11):2493S-2502S.
[13]Solymoss B C, Marcil M, Chaour M, et al. Fasting hyperinsulinism, insulin resistance syndrome, and coronary artery disease in men and women[J]. Am J Cardliol.1995; 76: 1152-1156.
[14]De Fronzo RA, Ferrannini E. A multifaced syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia and atherosclerotic cardiovascular disease[J]. Diabetes Care.
1991; 14:173-194.
[15]Reaven G M, Ho H. Sugar induced hypertension in Sprague Dawley rats[J]. Am J Hypertens, 1991,4:610-614.
[16]陈川,胡英华.胰岛素与高血压的关系[J].中华内科杂志,1992;31：354.
[17]Denker P S, Pollock V E. Fasting serum insulin levels in essential hypertension-A meta-analysis[J]. Arch Intern Med.1992; 152:1649-1651.
[18]Possemiers S, Grootaert C, Vermeiren J, et al. The intestinal environment in health and disease-recent insights on the potential of intestinal bacteria to influence human health[J]. Curr Pharm Des.2009; 15(18):2051-2065.
[19]S. Kolida, K. Tuohy, G. R. Gibson, Prebiotic effects of inulin and oligofructose[J]. Br J Nutr. 2002; 87(S2):S193-S 197.
[20]Catena C, Giacchetti G, Novello M, et al. Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension[J]. Am J Hypertens.2003; 16(11):973-978.
[21]Falkner B, Hulman S, Tannenbaum J, et al. Insulin resistance and blood pressure in young black men[J]. Hypertension.1990; 16(6):706-711.
[22]Brands M W, Hall J E, Keen H L. Is insulin resistance linked to hypenension?[J]. Clinical and Experimental and Phamacology and Physiology,1998,25(1):70-76.
[23]Taek C J, Smits P, Willemsen J, et al. Effects of insulin on vascular tone and sympathetic nervous system in NIDDM[J]. Diabetes.1996; 45(1):15-22.
[24]Zemel M B. Insulin resistance vs. hyperinsulinemia in hypertension:insulin regulation of Ca2+ transport and Ca2+ -regulation of insulin sensitivity[J]. J Nutr.1995; 125:1738-1743.
[25]Slater E. Insulin resistance and hypertension[J]. Hypertension.1991; 18(3):S1108-1114.
[26]Zemel M B, Bedford B A, Zemel P C, et al. Altered cation transport in non-insulin-dependent diabetic hypertension:effects of dietary calcium[J]. J Hypertens.1988,6(4):S228-230.
[27]Nagai M, Kamide K, Rakugi H, et al. Role of endothelin-1 induced by insulin in the regulation of vascular cell growth[J]. Am J Hypertens,2003,16:223-228.
[28]Dhalla NS, Temsah RM, Netticadan T. Role of oxidative stress in cardiovascular diseases[J]. J Hypertens,2000,18:655-673.
[29]Frank H J, Levin E R, Hu R M. et al. Insulin stimulates endothelin binding and action on cultured vascular smooth muscle cells[J]. Endocrinology.1993; 133(3):1092.
[30]陈颜芳,韩启德.胰岛素抵抗大鼠血.压升高的血管机制[J].中国病理生理杂志.1998;14(5)：458-461.
[31]Axelrod L. Insulin, prostaglandins, and the pathogenesis of hypertension[J]. Diabetes.1991; 10:1223-1227.
[32]Zarjevski N, Cusin I, Vettor R, et al. Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity[J]. Endocrinology.1993,133(4):1753-1758.
[33]Han JR, Deng B, Sun J. Effects of dietary medium-chain triglyceride on weight loss and
insulin sensitivity in a group of moderately overweight free-living type 2 diabetic Chinese subjects [J]. Metabolism.2007,56(7):985-991.
[34]王绍云,宋怀东,李荣英.高脂大鼠抵抗素基因的上调表达及与胰岛素、瘦素的相关性[J].中华内分泌代谢杂志,2003,19(3).
[35]DeFronzo RA. Dysfunctional fat cells, lipotoxicity and type 2 diabetes[J]. Int J Chn Pract, 2004; 143(Suppl):9-21.
[36]Heilbronn L, Smith SR, Ravussin E. Failure of fat cell proliferation, mitochondrial function and fat oxidation results in ectopic fat storage, insulin resistance and type 2 diabetes melitus[J]. Int J Obes Relat Metab Disord,2004; 28(Suppl 4):S12-21.
[37]Fukuhara A, Matsuda M, Nishizawa M, et al. Visfatin:a protein secreted by visceral fat that mimics the effects of insulin[J]. Science.2005; 307(5708):426-430.
[38]Chen MP, ChungFM, Chang DM, et al. Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus[J]. J Clin Endocrinol Metab, 2006; 91(1):295-299.
[39]Ognjanovic S, Bryant Greenwood GD. Pre-B-cell colony-enhancing factor, a novel cytokine of human fetal membranes[J]. Am J Obstet Gynecol.2002; 187(4):1051-1058.
[40]Delzenne NM, Daubioul C, Neyrinck M, et al. Inulin and oligofructose modulate lipid metabolism in animals:review of biochemical events and future prospects[J]. Br J Nutr. 2002;87:S255-259.
[41]Kok N, Morgan L, Williams C, et al. Insulin, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide and insulin-like growth factor I as putative mediators of the hypolipidemic effect of oligofructose in rats[J]. J Nutr.1998; 128:1099-1103.
[42]Daubioul C, De Wispelaere L, Taper H, et al. Dietary oligofructose lessens hepatic steatosis, but does not prevent hypertriglyceridemia in obese Zucker rats[J]. J Nutr.2000; 130:1314-1319.
[43]Oku T, Tokunaga T, Hosoya N. Non digestibility of a new sweetener "Neosugar" in the rat[J]. J Nutr.1984; 114:1574-81.
[44]Gibson G, Roberfroid M, Colonic microbiota, nutrition and health[M]. The Netherlands: Kluwer Academic Publishers,1999:55-70.
[45]Delzenne NM, Daubioul C, Neyrinck M, et al. Inulin and oligofructose modulate lipid metabolism in animals:review of biochemical events and future prospects[J]. Br J Nutr.2002; 87:S255-259.
[46]Delzenne N, Kok N, Deloyer P, et al. Polyamines as mediators of physiological effects of dietary oligofructose in rats[J]. J Nutr.2000; 130:2456-2460.
[47]Drucker DJ. Biological actions and therapeutic potential of the glucagons-like peptides[J]. Gastroenterology.2002; 122:531-544.
[48]Sakata I, Nakamura K, Yamazaki M, et al. Ghrelin-producing cells exist as two types of cells, closed-and opened-type cells, in the rat gastrointestinal tract[J]. Peptides.2002; 23:531-536.
[1]张璐,孔灵芝,预防慢性病：一项至关重要的投资——世界卫生组织报告[J].中国慢性病预防与控制.2006;14(1)：1-4.
[2]He J, Gu D, Chen J, et al. Premature deaths attributable to blood pressure in China:a prospective cohort study[J]. Lancet.2009; 374(9703):1765-1772.
[3]Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure[J]. Hypertension.2003; 42(6):1206-1252.
[4]Wang L, Kong L, Wu F, et al. Preventing chronic diseases in China[J]. Lancet.2005; 366(9499):1821-1824.
[5]Stevens VJ, Obarzanek E, Cook NR, et al. Long-term weight loss and changes in blood pressure:results of the Trials of Hypertension Prevention, Phase Ⅱ[J]. Ann Intern Med.2000; 134:1-11.
[6]Kiely AE, Kwatra SG, Kwatra MM. Treating prehypertension:medically sound and economically viable[J]. Blood Press.2009; 18(6):300-303.
[7]中国高血压防治指南(修订版).中华人民共和国卫生部.2005.
[8]Whitworth JA; World Health Organization, International Society of Hypertension Writing Group.2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension[J]. J Hypertens.2003; 21(11):1983-1992.
[9]Appel L J, Moore T J, Obarzanek E, etal, A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group[J]. N Engl J Med.1997, 336(16):1117-24.
[10]Appel LJ, Champagne CM, Harsha DW, Effects of comprehensive lifestyle modification on blood pressure control:main results of the PREMIER clinical trial[J]. JAMA.2003; 289(16):2083-2093.
[11]Burke V, A lifestyle programme for treated hypertensive improved health-related behaviours and cardiovascular risk factors, a randomized controlled trial[J]. Journal of Clinical Epidemiology.2007,60:133-141.
[12]Gibson GR, Roberfroid MB. Dietary modulation of the colonic microbiota:Introducing the concept of prebiotics[J]. J Nutr.1995; 125(6):1401-1412.
[13]Marcel B Roberfroid. Inulin-Type Fructans:Functional Food Ingredients[J]. J Nutr.2007;
137(11):2493S-2502S.
[14]Roberfroid MB. Functional foods:concepts and application to inulin and Oligofructose[J]. Br J Nutr.2002; 87(Suppl 2):S139-143.
[15]Rault-Nania MH, Demougeot C, Gueux E, et al. Inulin supplementation prevents high fructose diet-induced hypertension in rats[J]. Clin Nutr.2008; 27(2):276-282.
[16]Busserolles J, Gueux E, Rock E, Oligofructose protects against the hypertriglyceridemic and pro-oxidative effects of a high fructose diet in rats[J]. J Nutr.2003; 133(6):1903-1908.
[17]The Seventh Report of the Joint National Committee on High Blood Pressure (JNC-7),2003.
[18]O'Brien E. Blood pressure measurement:recommendations of the British Hypertension Society 3rd edition[M]. London:BMJ Publishing Group; 1997.
[19]Amorim PR, de Faria RC, Byrne NM, et al. Physical activity and nutritional status of children of low socioeconomic status. Two interrelated problems:undernutrition and overweight[J]. Asia Pacific Journal of Clinical Nutrition.2006; 15:2172-23.
[20]Qu NN, Li KJ. Study on reliability and validity of the IPAQ Chinese version[J]. Chinese Journal of Epidemiology.2004; 25(3):265-268.
[21]Shu XO, et al. Validity and reproducibility of the food frequency questionnaire used in the Shanghai Women's Health Study[J]. European Journal of Clinical Nutrition.2004; 58:17-23.
[22]Ware J, Kosinski M, Keller S. A 12-item short-form health survey:Construction of scales and preliminary tests of reliability and validity[J]. Medical Care.1996; 34(3):220-233.
[23]Lin JD, et al.24 h ambulatory blood pressure among 200 middle-aged and old people[J]. Chinese Journal of Cardiovascular Rehabilitation Medicine 2000,9(2):24-26.
[24]Guidelines on Prevention and Treatment of Hypertension in China.
[25]Appel LJ, et al.:A clinical trial of the effects of dietary patterns on blood pressure[J]. N Engl J Med.1997,336:1117-24.
[26]Trials of Hypertension Collaborative Research Group:Effects of weight loss and sodium reduction intervention on blood pressure incidence in overweight people with high-normal blood pressure:the trials of hypertension prevention (phase 2) [J]. Arch Intern Med 1997, 157:657-667.
[27]Kelley G, McClellan P. Antihypertensive effects of aerobic exercise. A brief meta-analytic review of randomized controlled trials[J]. Am J Hypertens.1994; 7(2):115-119.
[28]Kokubo Y, Kamide K. High-normal blood pressure and the risk of cardiovascular disease. Circ J.2009; 73(8):1381-1385.
[29]Germino FW. JNC 8:expectations, challenges, and wishes-a primary care perspective[J]. J Clin Hypertens (Greenwich).2009; 11(10):573-576.
[1]Gibson. G. R. Invitro and In vivo effects of oligofructose and Inulin on the colonic microbiota, in ORAFTI 1st ORAFTI Research conference proceedings 1995(Brussels)
[2]熊德鑫,近代微生态学,北京：中国科技出版社,2000.
[3]郭兴华,益生菌,北京：北京科技出版社.2002.
[4]Hidaka. H, Effects of Fructooligo saeeharides on Intestinal Flora[J], Bifidobacteria Microflora,1986:5(1)37-50
[5]Beghin Meigi, "Actilighf"Introduction the world's first health ingredient 2002
[6]张田珍,木寡糖特性和生理功能[J],食品工业月刊,2001：33(6)12
[7]罔田茂寿等,工业用糖质酵素Handbook,东京：相谈社Scientific,1999,113-146
[8]Yoji Iikura, Food Allergy and Liver Function——preventive Effects of Drugs and Directory Fructoligo saccharides[J]. Bioscience Microflora.2002:21(1)69-72
[9]Yamashita. K, Effects of Fructooligosaccharides on blood glucose and serum lipids In Diabetic subjects[J], Nutr Research,1984:(4) 961
[10]Ham. Y, Studies on Relationship between Intake of FOS and Abdominal symptoms [J], Geriatric Medicine,1985:23(5)817-828
[11]Ohm. A, Effect of FOS and other saccharides on Ca, Mg and P absorption in rate[J], Jap Soc Nutr Food Sci,46,123-129
[1]张璐,孔灵芝,预防慢性病：一项至关重要的投资——世界卫生组织报告[J].中国慢性病预防与控制.2006;14(1):1-4.
[2]于修成.循证医学与医疗卫生决策[J].中国循证医学.2001;1:1-2.
[3]2003 World Health Organization(WHO)/International Society of Hypertension(ISH) statement on management of hypertension[J]. J Hypertens,2003,21(11):1983-1992.
[4]Paulk, Whehon MD, Lawrence A, et al. The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels. Results of the trials of hypertension prevention, phase I[J]. JAMA.1992; 267:1213-1220.
[5]Stevens VJ, Obarzanek E, Cook NR, et al. Long-term weight loss and changes in blood pressure:results of the Trials of Hypertension Prevention, Phase II[J]. Ann Intern Med.2000; 134: 1-11.
[6]Paulk. Whehon, Lawrence J, et al. Sodium reduction and weight loss in the treatment of hypertension in older persons[J]. JAMA.1998; 279:839-846.
[7]The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Presure[J]. JAMA.2003; 289:2560-2572.
[8]Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood presure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet[J]. N Engl J Med.2001; 344:3-10.
[9]Miller ER, Erlinger TP, Young DR, et al. Results of the Diet, Exercise and Weight Loss Intervention Trial (DEW-IT)[J]. Hypertension.2002; 40:612-618.
[10]Edgar R. Miller, Thomas P. Ertinger, et al. Writing Group of the PREMIER Colaborative Research Group. Effects of comprehensive lifestyle modification on blood pressure control:main results of the PREMIER clinical trial[J]. JAMA.2003; 289:2083-2093.
[11]Herbert G. Langford, Barry R. Davis, Donald B laufox, et al. Effect of drug and diet treatment of mild hypertension on diastolic blood pressure[J]. Hypertension.1991; 17:210-217.
[12]Sylvia wassertheil Smoller, M. Donald Blaufox, Albert Oberman, et al. The trial of antihypertensive interventions and management(TAIM) study[J]. Arch Intern Med.1992; 152: 131-136.
[13]Sylvia wasseaheil smoller, Donald Blaufox, Albert Oberman, et al. Effect of antihypertensives on sexual function and quality of life:the TAIM study[J]. Ann Intern Med,1991; 114:613-620.
[14]Victor J. Stevens, Eva Obarzanek, Manly R. Sid, et al. Long term weight loss and changes in blood pressure:results of the trials of hypertension prevention, phase II [J]. Ann Intern Med.2001; 134:1-11.
[15]Brand M, Mulrow C, Lom J, et al. Nonpharmaeological therapy of Hypertension on elderly[C]. Cochrane Library.2000.