本文選題：膳食 + 脂肪酸��； 參考：《浙江大學(xué)》2016年博士論文

【摘要】：研究背景：原發(fā)性高血壓是遺傳因素和環(huán)境因索相互作用引起的一種全身代謝紊亂狀態(tài),腎素-血管緊張素系統(tǒng)(RAS)及其下游絲裂原活化蛋白激酶(MAPK)信號通路異�；罨c高血壓的發(fā)生、發(fā)展和轉(zhuǎn)歸密切相關(guān)。增加膳食n-3脂肪酸攝入可以顯著降低西方高血壓人群收縮壓和舒張壓,但尚缺乏膳食n-3脂肪酸對中國高血壓人群的隨機對照試驗研究。因此,目前并不清楚膳食n-3脂肪酸在中國人群中的降血壓作用以及其對RAS及其下游MAPK信號通路調(diào)控。目的與方法：為明確膳食n-3脂肪酸在中國人群中的降血壓作用及其可能機制,本研究通過薈萃分析,橫斷面研究,病例-對照研究、隨機臨床對照試驗和動物模型實驗,系統(tǒng)研究膳食n-3脂肪酸的在中國人群中的降血壓作用及其對RAS-MAPK信號通路的影響：(1)循證薈萃分析探索膳食n-3脂肪酸及其生物學(xué)標(biāo)志物在高血壓和其它慢性病發(fā)生、發(fā)展中的規(guī)律；(2)橫斷面研究探索n-3脂肪酸循環(huán)生物標(biāo)記物與高血壓患病率的關(guān)聯(lián)性；(3)病例-對照研究結(jié)合組學(xué)數(shù)據(jù)處理與分析技術(shù),辨認(rèn)高血壓-健康人群間血清肪酸差異標(biāo)志物；(4)隨機對照試驗研究膳食n-3脂肪酸對內(nèi)蒙高血壓人群血壓和其它心血管風(fēng)險因子的影響；(5)動物實驗研究膳食n-3脂肪酸對主動脈RAS系統(tǒng)及其下游MAPK信號通路的影響。結(jié)果：薈萃分析顯示,長鏈n-3脂肪酸生物學(xué)標(biāo)志物分別與高血壓、缺血性腦卒中和大腸癌顯著負(fù)相關(guān),膳食中n-3/n-6脂肪酸比例與女性乳腺癌發(fā)病風(fēng)險呈顯著負(fù)相關(guān)關(guān)系。橫斷面研究顯示,控制年齡、性別、體質(zhì)指數(shù)、吸煙、飲酒、運動、鹽的攝入等生活方式及心率、血脂和空腹血糖等臨床參數(shù)后,低血清22：6n-3、△5-去飽和酶指數(shù)(20：4n-6/20：3n-6)以及高16：0、16：1n-7和△6-去飽和酶指數(shù)(18：2n-6/18：3n-6)與高血壓患病率升高顯著相關(guān)。在病例-對照研究中,血清脂肪酸譜模式分析顯示血清22：6n-3和16：1n-7是區(qū)分高血壓病例-健康對照人群顯著差異脂肪酸標(biāo)志物,校正生活方式和臨床參數(shù)等混淆因子后,高血壓風(fēng)險與血清22：6n-3顯著負(fù)相關(guān),而與16：1n-7顯著正相關(guān)。通過90天深海魚油、亞麻籽油和玉米油對內(nèi)蒙地區(qū)高血壓患者進行隨機對照干預(yù)實驗發(fā)現(xiàn),魚油干預(yù)后舒張壓、胰島素抵抗指數(shù)和血清超敏C反應(yīng)蛋白水平均顯著下降,而玉米油和亞麻籽油組無顯著性變化；魚油組和亞麻籽油組能夠顯著降低血清同型半胱氨酸、總膽固醇和低密度脂蛋白水平,且降低值顯著低于玉米油組。在6周不同膳食油脂對自發(fā)高血壓大鼠(SHR)干預(yù)實驗研究中,發(fā)現(xiàn)膳食長鏈n-3脂肪酸可以顯著降低SHR大鼠尾動脈收縮壓、心率、血清總膽固醇、血漿AngⅡ和AngⅡ/Ang(1-7)比值,抑制主動脈組織血管緊張素轉(zhuǎn)化酶mRNA表達(dá)、降低p-Erk和P-38MAPK蛋白水平,并顯著增加主動脈組織Mas受體mRNA表達(dá)和改善主動脈重塑。結(jié)論：血清長鏈n-3脂肪酸與中國人群原發(fā)性高血壓患病率呈負(fù)相關(guān)關(guān)系,特別是22：6n-3；增加膳食長鏈n-3脂肪酸攝入可以降低中國高血壓人群心血管風(fēng)險因子,這可能與膳食n-3脂肪酸糾正腎素-血管緊張素系統(tǒng)失衡及其抑制下游MAPK磷酸化蛋白水平表達(dá)有關(guān)。本研究提示,增加膳食長鏈n-3脂肪酸攝入對中國人群中具有降血壓作用,能夠改善糖和脂肪代謝,為中國人群高血壓及其并發(fā)癥營養(yǎng)防治提供新的靶點和實驗依據(jù)。此研究結(jié)論尚需要在中國人群中開展多中心的隨機對照實驗去證實。
[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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R544.1
，

本文編號：2032285