膳食n-3脂肪酸在中国人群中的降血压作用及机制研究

发布时间：2018-06-17 20:03

  本文选题：膳食 + 脂肪酸　； 参考：《浙江大学》2016年博士论文

【摘要】：研究背景：原发性高血压是遗传因素和环境因索相互作用引起的一种全身代谢紊乱状态,肾素-血管紧张素系统(RAS)及其下游丝裂原活化蛋白激酶(MAPK)信号通路异常活化与高血压的发生、发展和转归密切相关。增加膳食n-3脂肪酸摄入可以显著降低西方高血压人群收缩压和舒张压,但尚缺乏膳食n-3脂肪酸对中国高血压人群的随机对照试验研究。因此,目前并不清楚膳食n-3脂肪酸在中国人群中的降血压作用以及其对RAS及其下游MAPK信号通路调控。目的与方法：为明确膳食n-3脂肪酸在中国人群中的降血压作用及其可能机制,本研究通过荟萃分析,横断面研究,病例-对照研究、随机临床对照试验和动物模型实验,系统研究膳食n-3脂肪酸的在中国人群中的降血压作用及其对RAS-MAPK信号通路的影响：(1)循证荟萃分析探索膳食n-3脂肪酸及其生物学标志物在高血压和其它慢性病发生、发展中的规律；(2)横断面研究探索n-3脂肪酸循环生物标记物与高血压患病率的关联性；(3)病例-对照研究结合组学数据处理与分析技术,辨认高血压-健康人群间血清肪酸差异标志物；(4)随机对照试验研究膳食n-3脂肪酸对内蒙高血压人群血压和其它心血管风险因子的影响；(5)动物实验研究膳食n-3脂肪酸对主动脉RAS系统及其下游MAPK信号通路的影响。结果：荟萃分析显示,长链n-3脂肪酸生物学标志物分别与高血压、缺血性脑卒中和大肠癌显著负相关,膳食中n-3/n-6脂肪酸比例与女性乳腺癌发病风险呈显著负相关关系。横断面研究显示,控制年龄、性别、体质指数、吸烟、饮酒、运动、盐的摄入等生活方式及心率、血脂和空腹血糖等临床参数后,低血清22：6n-3、△5-去饱和酶指数(20：4n-6/20：3n-6)以及高16：0、16：1n-7和△6-去饱和酶指数(18：2n-6/18：3n-6)与高血压患病率升高显著相关。在病例-对照研究中,血清脂肪酸谱模式分析显示血清22：6n-3和16：1n-7是区分高血压病例-健康对照人群显著差异脂肪酸标志物,校正生活方式和临床参数等混淆因子后,高血压风险与血清22：6n-3显著负相关,而与16：1n-7显著正相关。通过90天深海鱼油、亚麻籽油和玉米油对内蒙地区高血压患者进行随机对照干预实验发现,鱼油干预后舒张压、胰岛素抵抗指数和血清超敏C反应蛋白水平均显著下降,而玉米油和亚麻籽油组无显著性变化；鱼油组和亚麻籽油组能够显著降低血清同型半胱氨酸、总胆固醇和低密度脂蛋白水平,且降低值显著低于玉米油组。在6周不同膳食油脂对自发高血压大鼠(SHR)干预实验研究中,发现膳食长链n-3脂肪酸可以显著降低SHR大鼠尾动脉收缩压、心率、血清总胆固醇、血浆AngⅡ和AngⅡ/Ang(1-7)比值,抑制主动脉组织血管紧张素转化酶mRNA表达、降低p-Erk和P-38MAPK蛋白水平,并显著增加主动脉组织Mas受体mRNA表达和改善主动脉重塑。结论：血清长链n-3脂肪酸与中国人群原发性高血压患病率呈负相关关系,特别是22：6n-3；增加膳食长链n-3脂肪酸摄入可以降低中国高血压人群心血管风险因子,这可能与膳食n-3脂肪酸纠正肾素-血管紧张素系统失衡及其抑制下游MAPK磷酸化蛋白水平表达有关。本研究提示,增加膳食长链n-3脂肪酸摄入对中国人群中具有降血压作用,能够改善糖和脂肪代谢,为中国人群高血压及其并发症营养防治提供新的靶点和实验依据。此研究结论尚需要在中国人群中开展多中心的随机对照实验去证实。
[Abstract]:Background: essential hypertension is a systemic metabolic disorder caused by the interaction of genetic factors and environmental factors. The abnormal activation of the renin angiotensin system (RAS) and its downstream mitogen activated protein kinase (MAPK) signaling pathway is closely related to the occurrence of hypertension, development and prognosis. The increase of dietary n-3 fatty acid intake is increased. It can significantly reduce systolic and diastolic pressure in Western hypertensive people, but there is still a lack of randomized controlled trial study of dietary n-3 fatty acids for Chinese hypertensive people. Therefore, it is not clear that the antihypertensive effect of dietary n-3 fatty acids in Chinese people and its regulation of RAS and its downstream MAPK signaling pathway. The effect of dietary n-3 fatty acids on blood pressure reduction and its possible mechanism in Chinese population. This study was conducted by meta-analysis, cross-sectional study, case control study, randomized clinical trial and animal model experiment to systematically study the effect of dietary n-3 fatty acids on blood pressure in Chinese population and its effect on RAS-MAPK signaling pathway: (1) A meta analysis to explore the regularity of dietary n-3 fatty acids and their biological markers in the development of hypertension and other chronic diseases; (2) a cross-sectional study was conducted to explore the association of n-3 fatty acid circulating biomarkers with the prevalence of hypertension; (3) case control study combined with data processing and analysis techniques, to identify hypertension and health. The difference markers of serum fatty acids between people; (4) the effects of dietary n-3 fatty acids on blood pressure and other cardiovascular risk factors in Inner Mongolia hypertensive population, and (5) the effect of dietary n-3 fatty acids on the aortic RAS system and its downstream MAPK signaling pathway. Results: a meta-analysis showed long chain n-3 fat Acid biomarkers were negatively correlated with hypertension, ischemic stroke and colorectal cancer. The proportion of n-3/n-6 fatty acids in the diet was negatively correlated with the risk of breast cancer in women. A cross-sectional study showed that the control of age, sex, body mass index, smoking, drinking, exercise, salt intake and other lifestyle and heart rate, blood lipid and empty. The low serum 22:6n-3, Delta 5- desaturase index (20:4n-6/20:3n-6) and high 16:0,16:1n-7 and delta 6- desaturase index (18:2n-6/18:3n-6) were significantly related to the increase in the prevalence of hypertension. In case control studies, serum fatty acid pattern analysis showed that serum 22:6n-3 and 16:1n-7 were regions of serum 22:6n-3 and 16:1n-7. The risk of hypertension was significantly negatively correlated with the serum 22:6n-3 and significant positive correlation with 16:1n-7. The 90 day deep sea fish oil, flax seed oil and corn oil were used in a randomized controlled trial of hypertensive patients in Inner Mongolia area. The pre experiment showed that the diastolic pressure, the insulin resistance index and the serum hypersensitivity C reaction protein level decreased significantly after the fish oil intervention, but there was no significant change in the corn oil and flax seed oil group, and the fish oil group and flax seed oil group could significantly reduce the serum homocysteine, total cholesterol and low density lipoprotein levels, and the reduction value was significantly lower than that of the oil group. In the corn oil group, in the experimental study of spontaneous hypertensive rats (SHR) in 6 weeks, the dietary long chain n-3 fatty acids could significantly reduce the systolic pressure, heart rate, serum total cholesterol, the ratio of Ang II to Ang II /Ang (1-7) in SHR rats, and the inhibition of the expression of angiotensin converting enzyme mRNA in the main arterial tissue, and the reduction of p-Erk and P. -38MAPK protein level significantly increased the expression of Mas receptor mRNA in aortic tissue and improved aortic remodeling. Conclusion: Serum long chain n-3 fatty acids are negatively correlated with the prevalence of primary hypertension in Chinese people, especially in 22:6n-3; increased dietary long chain n-3 fatty acid intake can reduce cardiovascular risk factors in Chinese hypertensive people. This may be associated with the dietary n-3 fatty acid correction of the renin angiotensin system imbalance and its inhibition of the level of downstream MAPK phosphorylation. This study suggests that increasing dietary long chain n-3 fatty acid intake can reduce blood pressure in Chinese people, improve glucose and fat metabolism, and provide nutritional prevention for hypertension and its complications in Chinese population Conclusion this study still needs a multicenter randomized controlled trial in Chinese population.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R544.1
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本文编号：2032285