蓝莓花色苷对细颗粒物致机体心血管损伤的干预及其机制研究
发布时间：2018-07-24 16:24
【摘要】：目的通过动物实验和人群观察,评价蓝莓花色苷对细颗粒物(Fine particulate matter,PM_(2.5))暴露致机体心血管功能损伤的干预效果,并探讨相关机制,为我国PM_(2.5)暴露致心血管损伤易感人群的营养干预提供科学依据。方法1.人群试验⑴冠心病患病率及其影响因素调查采用横断面研究,调查天津市养老院218名老人冠心病患病率,并分析其影响因素。⑵蓝莓冻干粉对PM_(2.5)暴露冠心病老人心血管损伤的干预作用招募筛查出的冠心病患者为研究对象,分为干预组(31人)和对照组(28人)。干预组老人服用蓝莓冻干粉冲剂10g/天,对照组饮用水,连续干预60天。干预期间测量研究对象的HRV,每周一次,同时监测室内PM_(2.5)及室外主要环境污染物的日均浓度;在干预起点及末点采集血样,检测血清中心肌酶活性—肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)和α羟丁酸脱氢酶(HBDH),炎性因子含量—超敏C反应蛋白(us-CRP)、肿瘤坏死因子(TNF-α)和白介素10(IL-10),氧化应激指标—丙二醛(MDA)和超氧化物歧化酶(SOD)。2.动物实验⑴大鼠心血管损伤模型的建立雄性SD大鼠24只,随机分为对照组、PM_(2.5)低剂量染毒组(10 mg/kg)、PM_(2.5)高剂量染毒组(20 mg/kg),每组8只大鼠。PM_(2.5)染毒组大鼠经气管滴注PM_(2.5)悬浮液,滴注量为1.5ml/kg,隔天1次,共3次,对照组气管滴注相同体积的生理盐水。末次暴露24h后,记录心率、心电图(ECG);测定血清及心肌组织中心肌酶活性(LDH、CK和CK-MB)。⑵蓝莓提取物对PM_(2.5)染毒大鼠心血管损伤的干预研究雄性SD大鼠40只,随机分为对照组、PM_(2.5)染毒组、PM_(2.5)暴露+蓝莓提取物低剂量组、PM_(2.5)暴露+蓝莓提取物中剂量组、PM_(2.5)暴露+蓝莓提取物高剂量组,每组8只大鼠。蓝莓干预组大鼠分别灌胃0.5 g/kg、1.0 g/kg和2.0 g/kg蓝莓提取物悬浮液5.0 ml/kg,对照组及PM_(2.5)染毒组大鼠灌胃相同体积的生理盐水,连续灌胃5周。第6周,PM_(2.5)染毒组及蓝莓干预组大鼠经气管滴注PM_(2.5)悬浮液10 mg/kg,滴注量为1.5 ml/kg,隔天1次,共3次。对照组大鼠气管滴注相同体积的生理盐水。末次暴露24h后,记录心率、心电图;检测心肌酶活性(LDH、CK和CK-MB)、炎症因子含量(CRP、IL-6和IL-10)、氧化应激指标(MDA和SOD)、血管内皮功能(ET-1和Ang-II)及心肌凋亡蛋白表达(Bax和Bcl-2);取心尖、主动脉进行HE染色分析。结果1.人群试验⑴218名老年人冠心病患病率及其影响因素调查调查对象冠心病患病率为35.32%,高血压、高血脂是其危险因素。⑵蓝莓冻干粉对PM_(2.5)暴露冠心病老人心血管功能的干预作用对照组研究对象的HRV与室内PM_(2.5)平均浓度密切相关(P0.05),PM_(2.5)平均浓度每升高1个SD(80.42μg/m3),HRV-LF下降43.14%(-56.94,-24.92),p-NN50下降39.42%(-46.80,-31.02),其余指标同样与PM_(2.5)浓度呈负相关;干预组研究对象的HRV与室内PM_(2.5)平均浓度无关(P0.05),PM_(2.5)平均浓度每升高1个SD(80.42μg/m3),HRV-LF增加10.89%(-8.02,33.68),p-NN50下降0.81%(-7.62,6.50)。与对照组比较,干预组老人血清CK-MB活性、us-CRP含量MDA含量显著下降(P0.05),IL-10含量、SOD活性显著增高(P0.05)。动物实验⑴大鼠心血管损伤模型的建立与对照组比较,PM_(2.5)染毒组大鼠心率显著下降(P0.05),心电图ST段与T波发生改变;血清CK、血清及心肌组织中CK-MB活性显著增高(P0.05)。⑵蓝莓提取物对PM_(2.5)染毒大鼠心血管损伤的干预研究与对照组比较,PM_(2.5)染毒组大鼠心率显著下降(P0.05),心电图异常,血清CK、血清和心肌组织中的CK-MB活性显著增高(P0.05);给予蓝莓提取物干预后,尤其是中剂量蓝莓提取物可抑制PM_(2.5)染毒致大鼠心血管急性毒性效应。与对照组比较,PM_(2.5)染毒组大鼠血清IL-6、CRP水平显著升高(P0.05),而IL-10含量显著降低(P0.05);血清及心肌组织中MDA含量显著增高(P0.05),而心肌组织中SOD活性显著降低(P0.05);血浆中内皮素1(ET-1),血管紧张素Ⅱ含量显著升高(P0.05);同时心肌组织中Bax相对表达量显著增加(P0.05),Bcl-2相对表达量显著下降(P0.05)。给予不同剂量蓝莓提取物干预后可部分逆转上述变化,中剂量干预组效果最好。各实验组大鼠心脏、主动脉未见明显病理学改变。结论1.蓝莓冻干粉干预可拮抗PM_(2.5)暴露诱导的冠心病老人HRV的降低及心肌酶活性的增高,机制可能与其抗氧化、抑制炎症反应的作用有关。2.蓝莓提取物干预可抑制PM_(2.5)急性染毒大鼠心血管损伤,机制与其抗氧化、抑制炎症反应、保护血管内皮及抗凋亡作用有关。
[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.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R151
本文编号：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.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R151
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