藍(lán)莓花色苷對(duì)細(xì)顆粒物致機(jī)體心血管損傷的干預(yù)及其機(jī)制研究
發(fā)布時(shí)間：2018-07-24 16:24
【摘要】：目的通過(guò)動(dòng)物實(shí)驗(yàn)和人群觀察,評(píng)價(jià)藍(lán)莓花色苷對(duì)細(xì)顆粒物(Fine particulate matter,PM_(2.5))暴露致機(jī)體心血管功能損傷的干預(yù)效果,并探討相關(guān)機(jī)制,為我國(guó)PM_(2.5)暴露致心血管損傷易感人群的營(yíng)養(yǎng)干預(yù)提供科學(xué)依據(jù)。方法1.人群試驗(yàn)⑴冠心病患病率及其影響因素調(diào)查采用橫斷面研究,調(diào)查天津市養(yǎng)老院218名老人冠心病患病率,并分析其影響因素。⑵藍(lán)莓凍干粉對(duì)PM_(2.5)暴露冠心病老人心血管損傷的干預(yù)作用招募篩查出的冠心病患者為研究對(duì)象,分為干預(yù)組(31人)和對(duì)照組(28人)。干預(yù)組老人服用藍(lán)莓凍干粉沖劑10g/天,對(duì)照組飲用水,連續(xù)干預(yù)60天。干預(yù)期間測(cè)量研究對(duì)象的HRV,每周一次,同時(shí)監(jiān)測(cè)室內(nèi)PM_(2.5)及室外主要環(huán)境污染物的日均濃度;在干預(yù)起點(diǎn)及末點(diǎn)采集血樣,檢測(cè)血清中心肌酶活性—肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脫氫酶(LDH)和α羥丁酸脫氫酶(HBDH),炎性因子含量—超敏C反應(yīng)蛋白(us-CRP)、腫瘤壞死因子(TNF-α)和白介素10(IL-10),氧化應(yīng)激指標(biāo)—丙二醛(MDA)和超氧化物歧化酶(SOD)。2.動(dòng)物實(shí)驗(yàn)⑴大鼠心血管損傷模型的建立雄性SD大鼠24只,隨機(jī)分為對(duì)照組、PM_(2.5)低劑量染毒組(10 mg/kg)、PM_(2.5)高劑量染毒組(20 mg/kg),每組8只大鼠。PM_(2.5)染毒組大鼠經(jīng)氣管滴注PM_(2.5)懸浮液,滴注量為1.5ml/kg,隔天1次,共3次,對(duì)照組氣管滴注相同體積的生理鹽水。末次暴露24h后,記錄心率、心電圖(ECG);測(cè)定血清及心肌組織中心肌酶活性(LDH、CK和CK-MB)。⑵藍(lán)莓提取物對(duì)PM_(2.5)染毒大鼠心血管損傷的干預(yù)研究雄性SD大鼠40只,隨機(jī)分為對(duì)照組、PM_(2.5)染毒組、PM_(2.5)暴露+藍(lán)莓提取物低劑量組、PM_(2.5)暴露+藍(lán)莓提取物中劑量組、PM_(2.5)暴露+藍(lán)莓提取物高劑量組,每組8只大鼠。藍(lán)莓干預(yù)組大鼠分別灌胃0.5 g/kg、1.0 g/kg和2.0 g/kg藍(lán)莓提取物懸浮液5.0 ml/kg,對(duì)照組及PM_(2.5)染毒組大鼠灌胃相同體積的生理鹽水,連續(xù)灌胃5周。第6周,PM_(2.5)染毒組及藍(lán)莓干預(yù)組大鼠經(jīng)氣管滴注PM_(2.5)懸浮液10 mg/kg,滴注量為1.5 ml/kg,隔天1次,共3次。對(duì)照組大鼠氣管滴注相同體積的生理鹽水。末次暴露24h后,記錄心率、心電圖;檢測(cè)心肌酶活性(LDH、CK和CK-MB)、炎癥因子含量(CRP、IL-6和IL-10)、氧化應(yīng)激指標(biāo)(MDA和SOD)、血管內(nèi)皮功能(ET-1和Ang-II)及心肌凋亡蛋白表達(dá)(Bax和Bcl-2);取心尖、主動(dòng)脈進(jìn)行HE染色分析。結(jié)果1.人群試驗(yàn)⑴218名老年人冠心病患病率及其影響因素調(diào)查調(diào)查對(duì)象冠心病患病率為35.32%,高血壓、高血脂是其危險(xiǎn)因素。⑵藍(lán)莓凍干粉對(duì)PM_(2.5)暴露冠心病老人心血管功能的干預(yù)作用對(duì)照組研究對(duì)象的HRV與室內(nèi)PM_(2.5)平均濃度密切相關(guān)(P0.05),PM_(2.5)平均濃度每升高1個(gè)SD(80.42μg/m3),HRV-LF下降43.14%(-56.94,-24.92),p-NN50下降39.42%(-46.80,-31.02),其余指標(biāo)同樣與PM_(2.5)濃度呈負(fù)相關(guān);干預(yù)組研究對(duì)象的HRV與室內(nèi)PM_(2.5)平均濃度無(wú)關(guān)(P0.05),PM_(2.5)平均濃度每升高1個(gè)SD(80.42μg/m3),HRV-LF增加10.89%(-8.02,33.68),p-NN50下降0.81%(-7.62,6.50)。與對(duì)照組比較,干預(yù)組老人血清CK-MB活性、us-CRP含量MDA含量顯著下降(P0.05),IL-10含量、SOD活性顯著增高(P0.05)。動(dòng)物實(shí)驗(yàn)⑴大鼠心血管損傷模型的建立與對(duì)照組比較,PM_(2.5)染毒組大鼠心率顯著下降(P0.05),心電圖ST段與T波發(fā)生改變;血清CK、血清及心肌組織中CK-MB活性顯著增高(P0.05)。⑵藍(lán)莓提取物對(duì)PM_(2.5)染毒大鼠心血管損傷的干預(yù)研究與對(duì)照組比較,PM_(2.5)染毒組大鼠心率顯著下降(P0.05),心電圖異常,血清CK、血清和心肌組織中的CK-MB活性顯著增高(P0.05);給予藍(lán)莓提取物干預(yù)后,尤其是中劑量藍(lán)莓提取物可抑制PM_(2.5)染毒致大鼠心血管急性毒性效應(yīng)。與對(duì)照組比較,PM_(2.5)染毒組大鼠血清IL-6、CRP水平顯著升高(P0.05),而IL-10含量顯著降低(P0.05);血清及心肌組織中MDA含量顯著增高(P0.05),而心肌組織中SOD活性顯著降低(P0.05);血漿中內(nèi)皮素1(ET-1),血管緊張素Ⅱ含量顯著升高(P0.05);同時(shí)心肌組織中Bax相對(duì)表達(dá)量顯著增加(P0.05),Bcl-2相對(duì)表達(dá)量顯著下降(P0.05)。給予不同劑量藍(lán)莓提取物干預(yù)后可部分逆轉(zhuǎn)上述變化,中劑量干預(yù)組效果最好。各實(shí)驗(yàn)組大鼠心臟、主動(dòng)脈未見明顯病理學(xué)改變。結(jié)論1.藍(lán)莓凍干粉干預(yù)可拮抗PM_(2.5)暴露誘導(dǎo)的冠心病老人HRV的降低及心肌酶活性的增高,機(jī)制可能與其抗氧化、抑制炎癥反應(yīng)的作用有關(guān)。2.藍(lán)莓提取物干預(yù)可抑制PM_(2.5)急性染毒大鼠心血管損傷,機(jī)制與其抗氧化、抑制炎癥反應(yīng)、保護(hù)血管內(nèi)皮及抗凋亡作用有關(guān)。
[Abstract]:Objective to evaluate the effects of blueberry anthocyanins on cardiovascular damage caused by Fine particulate matter (PM_ (2.5)) exposure by animal experiments and population observation, and to explore the relevant mechanisms for the nutritional intervention of the susceptible groups of cardiovascular injury induced by PM_ (2.5) exposure in China. Method 1. crowds test (1) crowns A cross-sectional study was used to investigate the incidence of coronary heart disease in 218 elderly elderly patients in Tianjin, and to analyze its influencing factors. (2) the intervention of blueberry freeze-dried powder on cardiovascular injury in elderly patients with PM_ (2.5) exposure to coronary heart disease (CAD) was recruited as an object of study, divided into intervention group (31) and the same Group (28 people). The elderly in the intervention group took the blueberry freeze-dried powder for 10g/ days and the control group drank water for 60 days. During the intervention period, the HRV of the research subjects was measured, and the daily concentration of the indoor PM_ (2.5) and the outdoor major environmental pollutants was monitored at the same time; the blood samples were collected at the starting point and the end point, and the serum cardiac muscle enzyme activity - creatine was detected. Kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH) and alpha hydroxybutyrate dehydrogenase (HBDH), inflammatory factor content - hypersensitive C reactive protein (us-CRP), tumor necrosis factor (TNF- a) and interleukin 10 (IL-10), oxidative stress markers - malondialdehyde (MDA) and superoxide dismutase (SOD).2. animal experiment (1) model of cardiovascular injury in rats 24 male SD rats were randomly divided into control group, PM_ (2.5) low dose exposure group (10 mg/kg), PM_ (2.5) high dose exposure group (20 mg/kg),.PM_ (2.5) group of 8 rats in each group were dripped with PM_ (2.5) suspension via trachea, drip amount was 1.5ml/kg, 1 times every other day, 3 times, and the control group was dripped with the same volume of physiological saline. The last exposure 24h After that, heart rate and electrocardiogram (ECG) were recorded and serum and myocardial tissue center muscle enzyme activity (LDH, CK and CK-MB) were measured. (2) the intervention of blueberry extract on cardiovascular injury in PM_ (2.5) rats was studied in 40 male SD rats, randomly divided into control group, PM_ (2.5) exposure group, PM_ (2.5) exposure + blueberry extract low dose group, PM_ (2.5) exposure + blueberry extract Medium dose group, PM_ (2.5) exposure + blueberry extract high dose group, 8 rats in each group. The rats in the blueberry intervention group were treated with 0.5 g/kg, 1 g/kg and 2 g/kg blueberry extract suspension 5 ml/kg respectively. The control group and PM_ (2.5) rats were treated with the same volume of normal saline for 5 weeks. Sixth weeks, PM_ (2.5) and blueberry intervention group. PM_ (2.5) suspension was injected into the trachea of 10 mg/kg, the infusion amount was 1.5 ml/kg, 1 times a day, 3 times. The control group was injected with the same volume of normal saline. After the last exposure to 24h, the heart rate and electrocardiogram (LDH, CK and CK-MB), the content of inflammatory factors (CRP, IL-6 and IL-10), the oxidative stress index (MDA and SOD), intravascular The skin function (ET-1 and Ang-II) and the expression of cardiac apoptotic protein (Bax and Bcl-2), the apex of the heart and the HE staining of the aorta. Results 1. people were tested for the prevalence of coronary heart disease and its influencing factors in 218 elderly people. The prevalence rate of coronary heart disease was 35.32%, hypertension and hyperlipidemia were the risk factors. (2) the exposure of blueberry freeze-dried powder to PM_ (2.5) exposure The intervention of cardiovascular function of the elderly patients with coronary heart disease was closely related to the average concentration of HRV in the control group and the average concentration of PM_ (2.5) in the control group (P0.05), the average concentration of PM_ (2.5) increased by 1 SD (80.42 u g/m3), HRV-LF decreased by 43.14% (-56.94, -24.92), p-NN50 decreased by 39.42% (-46.80, -31.02), and the other indexes were also negatively correlated with the concentration of 2.5 (2.5); intervention group research The average concentration of HRV was not related to the average concentration of PM_ (2.5) in the laboratory (P0.05), the average concentration of PM_ (2.5) increased by 1 SD (80.42 g/m3), HRV-LF increased by 10.89% (-8.02,33.68) and p-NN50 decreased by 0.81% (-7.62,6.50). 05). In animal experiment (1), the establishment of the model of cardiovascular injury in rats was compared with the control group. The heart rate of PM_ (2.5) was significantly decreased (P0.05), the ST segment and the T wave in the electrocardiogram were changed; the serum CK, serum and myocardial CK-MB activity increased significantly (P0.05). (2) the intervention of blueberry extract on cardiovascular injury in PM_ (2.5) rats Compared with group PM_ (2.5), the heart rate decreased significantly (P0.05), abnormal electrocardiogram, serum CK, CK-MB activity in serum and myocardial tissue increased significantly (P0.05). The prognosis of blueberry extracts, especially the medium dose blueberry extract, could inhibit the acute cardiovascular toxicity of PM_ (2.5) infected rats. Compared with the control group, PM_ (2.5) dyed the blueberry. The serum level of IL-6 and CRP increased significantly (P0.05), while the content of IL-10 decreased significantly (P0.05), and the content of MDA in serum and myocardial tissue increased significantly (P0.05), and the activity of SOD in the myocardium was significantly decreased (P0.05); the plasma endothelin 1 (ET-1) and the blood vessel tight Zhang Su content increased significantly (P0.05); meanwhile, the relative expression of Bax in the myocardium was significant. With the increase of (P0.05), the relative expression of Bcl-2 decreased significantly (P0.05). After the intervention of different doses of blueberry extract, the above changes could be partly reversed. The effect of the middle dose intervention group was the best. No obvious pathological changes were found in the heart and aorta of the experimental group. Conclusion 1. blueberry freeze-dried powder intervention could antagonize the HRV of the coronary heart disease induced by PM_ (2.5). Decrease and increase the activity of myocardial enzymes, the mechanism may be related to the effect of anti oxidation and inhibition of inflammatory reaction. The intervention of.2. blueberry extract can inhibit the cardiovascular damage of PM_ (2.5) acute infected rats. The mechanism is related to its antioxidation, inhibition of inflammation, protection of vascular endothelium and the anti withering effect.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R151
本文編號(hào)：2141954
[Abstract]:Objective to evaluate the effects of blueberry anthocyanins on cardiovascular damage caused by Fine particulate matter (PM_ (2.5)) exposure by animal experiments and population observation, and to explore the relevant mechanisms for the nutritional intervention of the susceptible groups of cardiovascular injury induced by PM_ (2.5) exposure in China. Method 1. crowds test (1) crowns A cross-sectional study was used to investigate the incidence of coronary heart disease in 218 elderly elderly patients in Tianjin, and to analyze its influencing factors. (2) the intervention of blueberry freeze-dried powder on cardiovascular injury in elderly patients with PM_ (2.5) exposure to coronary heart disease (CAD) was recruited as an object of study, divided into intervention group (31) and the same Group (28 people). The elderly in the intervention group took the blueberry freeze-dried powder for 10g/ days and the control group drank water for 60 days. During the intervention period, the HRV of the research subjects was measured, and the daily concentration of the indoor PM_ (2.5) and the outdoor major environmental pollutants was monitored at the same time; the blood samples were collected at the starting point and the end point, and the serum cardiac muscle enzyme activity - creatine was detected. Kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH) and alpha hydroxybutyrate dehydrogenase (HBDH), inflammatory factor content - hypersensitive C reactive protein (us-CRP), tumor necrosis factor (TNF- a) and interleukin 10 (IL-10), oxidative stress markers - malondialdehyde (MDA) and superoxide dismutase (SOD).2. animal experiment (1) model of cardiovascular injury in rats 24 male SD rats were randomly divided into control group, PM_ (2.5) low dose exposure group (10 mg/kg), PM_ (2.5) high dose exposure group (20 mg/kg),.PM_ (2.5) group of 8 rats in each group were dripped with PM_ (2.5) suspension via trachea, drip amount was 1.5ml/kg, 1 times every other day, 3 times, and the control group was dripped with the same volume of physiological saline. The last exposure 24h After that, heart rate and electrocardiogram (ECG) were recorded and serum and myocardial tissue center muscle enzyme activity (LDH, CK and CK-MB) were measured. (2) the intervention of blueberry extract on cardiovascular injury in PM_ (2.5) rats was studied in 40 male SD rats, randomly divided into control group, PM_ (2.5) exposure group, PM_ (2.5) exposure + blueberry extract low dose group, PM_ (2.5) exposure + blueberry extract Medium dose group, PM_ (2.5) exposure + blueberry extract high dose group, 8 rats in each group. The rats in the blueberry intervention group were treated with 0.5 g/kg, 1 g/kg and 2 g/kg blueberry extract suspension 5 ml/kg respectively. The control group and PM_ (2.5) rats were treated with the same volume of normal saline for 5 weeks. Sixth weeks, PM_ (2.5) and blueberry intervention group. PM_ (2.5) suspension was injected into the trachea of 10 mg/kg, the infusion amount was 1.5 ml/kg, 1 times a day, 3 times. The control group was injected with the same volume of normal saline. After the last exposure to 24h, the heart rate and electrocardiogram (LDH, CK and CK-MB), the content of inflammatory factors (CRP, IL-6 and IL-10), the oxidative stress index (MDA and SOD), intravascular The skin function (ET-1 and Ang-II) and the expression of cardiac apoptotic protein (Bax and Bcl-2), the apex of the heart and the HE staining of the aorta. Results 1. people were tested for the prevalence of coronary heart disease and its influencing factors in 218 elderly people. The prevalence rate of coronary heart disease was 35.32%, hypertension and hyperlipidemia were the risk factors. (2) the exposure of blueberry freeze-dried powder to PM_ (2.5) exposure The intervention of cardiovascular function of the elderly patients with coronary heart disease was closely related to the average concentration of HRV in the control group and the average concentration of PM_ (2.5) in the control group (P0.05), the average concentration of PM_ (2.5) increased by 1 SD (80.42 u g/m3), HRV-LF decreased by 43.14% (-56.94, -24.92), p-NN50 decreased by 39.42% (-46.80, -31.02), and the other indexes were also negatively correlated with the concentration of 2.5 (2.5); intervention group research The average concentration of HRV was not related to the average concentration of PM_ (2.5) in the laboratory (P0.05), the average concentration of PM_ (2.5) increased by 1 SD (80.42 g/m3), HRV-LF increased by 10.89% (-8.02,33.68) and p-NN50 decreased by 0.81% (-7.62,6.50). 05). In animal experiment (1), the establishment of the model of cardiovascular injury in rats was compared with the control group. The heart rate of PM_ (2.5) was significantly decreased (P0.05), the ST segment and the T wave in the electrocardiogram were changed; the serum CK, serum and myocardial CK-MB activity increased significantly (P0.05). (2) the intervention of blueberry extract on cardiovascular injury in PM_ (2.5) rats Compared with group PM_ (2.5), the heart rate decreased significantly (P0.05), abnormal electrocardiogram, serum CK, CK-MB activity in serum and myocardial tissue increased significantly (P0.05). The prognosis of blueberry extracts, especially the medium dose blueberry extract, could inhibit the acute cardiovascular toxicity of PM_ (2.5) infected rats. Compared with the control group, PM_ (2.5) dyed the blueberry. The serum level of IL-6 and CRP increased significantly (P0.05), while the content of IL-10 decreased significantly (P0.05), and the content of MDA in serum and myocardial tissue increased significantly (P0.05), and the activity of SOD in the myocardium was significantly decreased (P0.05); the plasma endothelin 1 (ET-1) and the blood vessel tight Zhang Su content increased significantly (P0.05); meanwhile, the relative expression of Bax in the myocardium was significant. With the increase of (P0.05), the relative expression of Bcl-2 decreased significantly (P0.05). After the intervention of different doses of blueberry extract, the above changes could be partly reversed. The effect of the middle dose intervention group was the best. No obvious pathological changes were found in the heart and aorta of the experimental group. Conclusion 1. blueberry freeze-dried powder intervention could antagonize the HRV of the coronary heart disease induced by PM_ (2.5). Decrease and increase the activity of myocardial enzymes, the mechanism may be related to the effect of anti oxidation and inhibition of inflammatory reaction. The intervention of.2. blueberry extract can inhibit the cardiovascular damage of PM_ (2.5) acute infected rats. The mechanism is related to its antioxidation, inhibition of inflammation, protection of vascular endothelium and the anti withering effect.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R151
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10 劉曉倩;宋春華;李長(zhǎng)平;崔壯;魏鳳江;柯慧;朱寶;劉媛媛;馬駿;;天津市社區(qū)居民慢性病患病情況流行病學(xué)調(diào)查[J];中國(guó)衛(wèi)生統(tǒng)計(jì);2012年05期
，本文編號(hào)：2141954
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