冷空气活动对心脑血管疾病相关指标影响的初步研究
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摘要
心脑血管疾病目前已成为全球第一位死因,是严重的世界性公共卫生问题,也是严重威胁我国居民健康和社会发展的重大卫生问题之一,因此,积极探索心脑血管疾病的危险因素及其诱发机理,有效预防心脑血管疾病的发生和发展,最大限度地减少心脑血管疾病发病率和死亡率,成为21世纪医学及相关交叉学科共同关注的课题。大量研究表明,冷空气活动是心脑血管疾病发生的病因和急性发作的诱因之一,随着全球气候异常变化的加剧,极端冷事件的日趋增多,加之人们已逐渐适应了暖冬而对寒冷适应较脆弱的现实状况,致使冷空气活动对人群健康的影响会更加严重。故此,通过对冷空气活动与心脑血管疾病两者间关联性及其影响机理的深入研究,将有助于更好地预测和防止心脑血管疾病的发生、发展和意外。然而目前有关冷空气活动对心脑血管疾病影响的研究大多是建立在心脑血管患者流行病学数据定性分析的基础上,缺乏对人群心脑血管敏感指标变化的跟踪监测,并且冷空气活动时的主要气象因素剧烈变化对心脑血管系统的损害作用及程度的定量分析及其对心脑血管疾病发生和加重的影响机理方面的研究也很欠缺。为此,本研究从下列两方面开展了相关研究工作：(1)选择空气清洁、受冷空气影响较多的甘肃省张掖市为研究现场,于一次冷空气过境前、过境时和过境后对选取的研究对象进行血脂、儿茶酚胺(CA)、肌红蛋白(Mb)、心肌肌钙蛋白Ⅰ(cTnI)、血管内皮素-1(ET-1)和血液流变学等与心脑血管疾病发病相关的敏感指标(以下称敏感指标)进行测定。(2)利用人工气候箱模模拟与人群相似的冷空气过程和方法,分析正常Wistar大鼠和自发性高血压大鼠(SHR)的心率、收缩压、舒张压、血脂、CA、Mb、cTnI和ET-1水平在冷空气过程中的变化情况,由此分析各指标在冷空气活动时的变化程度与特征,探讨冷空气活动对心脑血管疾病影响的敏感指标和冷空气活动引起和诱发心脑血管疾病发生、发展及结局的可能机制,为心脑血管疾病的预防、治疗、预测及医疗气象预报服务等提供科学依据。主要结果如下：
1.人群实验结果
按照研究对象的遴选标准,最终确定病例30例,对照组40例,病例和对照的性别和年龄构成均无显著性差异(P>0.05)。
(1)血脂检测结果
病例组和对照组血脂7项在冷空气过境过程中变化无显著性差异(P>0.05)。在冷空气活动过程中,病例组的TC和LDL-C持续升高,HDL-C先降低后有所升高；对照组TC也持续升高,但LDL-C和HDL-C在过境时升高,过境后下降。上述各指标在冷空气前中后的变化均无显著性差异。
(2)儿茶酚胺检测结果
冷空气过境前、中、后三个时段病例组和对照组的DA水平均有显著差异(P<0.05),NE和AD水平无显著性差异(P>0.05)；在冷空气过程中,病例组DA水平持续下降,NE和AD水平呈持续上升趋势,而对照组的三项指标在冷空气过境时升高,过境后降低。
(3)心肌和血管蛋白检测结果
病例组的Mb、cTnI和ET-1水平以及对照组的Mb和ET-1水平在冷空气过境前、中、后三个阶段其变化均存在显著性差异(P<0.05)；冷空气过程中,病例组和对照组的Mb和cTnI均持续升高,但两组的ET-1则在冷空气过境时升高,过境后降低,且明显低于过境前。
(4)血液流变学检测结果
冷空气过境时,病例组和对照组的全血粘度低切(WBV-L)、中切值(WBV-M)、全血还原粘度低切(WBDV-L)、红细胞聚集指数(AI)和刚性指数(RI)均显著升高(P<0.05),除此之外,病例组全血还原粘度高切值(WBDV-H)和红细胞电泳指数(EI)也显著升高(P<0.05)。
2.动物实验结果
按照动物实验的伦理学要求,在人群现场研究时的实际气温变化基础上,将温度整体上调12.1℃,保持降温的幅度保持不变,作为动物实验的模拟气象条件。
(1)心率和血压检测结果
在冷空气模拟过程中,Wistar大鼠和SHR大鼠的心率先升高后降低,Wistar大鼠B组与A组比较差异显著(P<0.05),与此同时,Wistar大鼠的血压持续升高；SHR大鼠的血压先降低后略有升高,但仍低于A组,B组和C组与A组比较,血压变化均存在显著性差异(P<0.05)。
(2)血脂检测结果
Wistar大鼠A、B、C三组TG水平差异显著(P<0.05),C组明显低于A组和B组(P<0.05),SHR鼠的HDL-C(?)LDL-CB组明显高于A组和C组(P<0.05)；实验过程中,Wistar大鼠TC、TG和HDL-C均呈现持续降低趋势,而LDL-C则在降温时升高,降温后降低；SHR大鼠TC、HDL-C(?)LDL-C在降温时升高,降温后降低,TG则持续下降。
(3)儿茶酚胺类检测结果
进入冷空气模型后,Wistar大鼠和SHR大鼠A、B、C三组的DA水平差异显著(P<0.05); Wistar大鼠组的DA、NE和AD在降温时升高,降温后降低,但仍高于降温前；SHR大鼠DA在降温时降低,降温后升高,但低于降温前,NE和AD则持续下降。
(4)动物实验Mb、cTnl和ET-1检测结果
进入冷空气模型后,Wistar大鼠A、B、C三组的cTnl和ET-1水平差异显著(P<0.05),SHR大鼠A、B、C三组的ET-1差异显著(P<0.05)。实验过程中,Wistar大鼠Mb、cTnI和ET-1持续升高,SHR大鼠Mb、cTn和ET-1在降温时降低,温度回升时升高,但Mb和ET-1仍然低于降温前。
3.结论
(1)冷空气活动过程中,研究对象的血脂、儿茶酚胺、心肌蛋白和血管内皮素及血液流变学等反映心脑血管疾病发生、发展及严重程度的各指标均有变化、提示冷空气活动对对血管、心肌和心脏等心血管系统的影响是多层次、多途径的综合性影响。
(2)冷空气活动对病例组和对照组的影响程度不同,对心脑血管病人的影响比健康人群的影响更大。
(3)冷空气等气象因素不但是导致心脑血管疾病发生发展的直接病因之一,还作为诱因引发体内相关生理指标的分泌和代谢,从而导致疾病发生或出现不同结局。
(4)人群现场调查和动物实验结果均显示,冷空气过程所反映的特殊气象条件能引起机体DA和ET-1水平的显著变化,提示DA和ET-1是冷空气活动对心脑血管疾病影响最为敏感的指标。
(5)通过研究对象各指标的变化程度和趋势分析,初步认为冷空气活动影响心脑血管疾病的机制有：肾上腺髓质系统和血管内皮素应急机制。
(6)人群和动物在个别指标上有些许不同,提示由于种属的不同,将冷空气活动对动物实验的某些结果直接外推到人,还有待充分的论证,结论外推还得谨慎。
Cardio-vascular disease (CVD) has became the first cause of death and one of the serious worldwide public health problem, is also a great threat to the residents'health and social development of our country in recent years. So, exploring the risk factors, occurrence, deterioration and reducing morbidity and mortality of the CVD are the mutual interesting topic in medicine and related interdisciplinary filed in the21st century. A large number of studies have shown that the cold air activity is not only one of the causes of CVD, but also the main inducing cause of CVD acute attacks. With the global climate changes, the cold air affected area is expanding, the frequency of air activities is increasing, and the influence on the health of human been is aggravating, meanwhile, people have adapted to the warm winter and have weak adaptability to cold, the cold air activities will cause more serious hazards and influences to human. According to the reasons above, researching the relationship between cold air activities and CVD, will help to better predict and prevent of occurrence, development and accident of CVD in advance. However, the recent researches on the effects which cold air activities led to CVD were mostly based on the analysis of patients'epidemiological data, It has not been reported or rarely to detect the sensitive indicators of CVD, lacking of quantitative analyze of the effects, effective degree, and the influence mechanism of air condition related CVD as well the dramatic changes of main meteorological factors. For this purpose, two aspects research were carried out below:(1) The city of Zhangye of Gansu province was chosen as a good air quality but more likely affected area by cold air, then the Sensitive indicators associated closely with VCD, such as blood lipid, CA, Mb, cTn I, ET-1, hemorheology were detected before, during and after the cold air transit respectively.(2) The parallel test cold air process as the population was simulated in artificial climate box, and the variation of hart rate, Systolic pressure, diastolic blood pressure, blood lipid, CA, Mb, cTn I and ET-1of the Wistar rats and SHR rats were detected as the same as the crowd, from the data above, to analysis of the influence of cold air activity on CVD sensitive index and explore the possible mechanisms of occurrence, development and dead end, This will provide the basis for prevention, treatment and medical meteorological prediction on CVD care. The main results as follows:
1. Results of field trial
30cases and40controls were bring into the research according to the experimental demand, and tow groups had no significant difference (P>0.05) in gender and age.
(1) Blood lipid test results
Seven items of blood lipid index of Cases and controls had no significant difference during the whole cold air process. And TC and LDL-C continue to rise and HDL-C to decline in the process of cold air activity. TC in the control group continue to rise and LDL and HDL-C lift in the cold air activity then fall after cold air activity. And the changes had no significant difference (P>0.05).
(2) Results of CA
The DA of cases and controls had notable changes before, during and after the cold air activity, statistics test had significant difference (P<0.05) while NE and AD had not. In the whole process, DA level continued to decline, NE and AD kept a trend of rising, while the control group of three indicators is elevated during the activity and reduction after the cold air activity.
(3) Results of Mb, cTnI and ET-1
The Mb, cTnI and ET-1of cases group and the Mb and ET-1of control group had notable changes (P<0.05) before, during and after the cold air activity; Mb and cTnI of case group and the control group continued to rise in the process of cold air transit and the ET-1rise first and then decline to a low level even low than before.
(4) Results of hemorheology
During the cold air activity, the Whole Blood Viscosity (low, middle shear rate), Whole Blood Deoxidize Viscosity (low shear rate), Assembling Index (AI) and Rigidity index (RI) levels of cases and controls increased significantly (P<0.05), and the Whole Blood Deoxidize Viscosity High shear rate (WBDV-H) and Electrophoresis Index (El) raised and the same time..
2. The results of animal experimental
According with the requirements for the ethics of animal experiments, based on the basis of field trail studies, kept the change tendency after lifting12.1℃as animal experiments simulated meteorological conditions.
(1) Test results of the heart rate and blood pressure
During the simulation, the heart rate of SHR and Wistar rats increased when the temperature drop down, and then slowed down with the temperature gradually returned to normal. The blood pressure of Wistar rats groups kept rising, but no significant difference compared with basic values, and the blood pressure of SHR rats groups speed up first then slow down, there were significant differences (P<0.05).
(2) Blood lipid test results
There were significant differences (P<0.05) between TG of A, B, C of Wistar rat group, and the TG of group C was lower than that in group A and group B (P<0.05), The HDL and LDL-C of SHR rats in group B was significantly higher in group A and group C (P<0.05); in the Experiments, TC, TG and HDL-C of Wistar rats kept a trend of decrease, while the LDL-C increase when the temperature reduce and decrease after the drop, The TC, HDL-C and LDL-C of SHR rats rised when temperature cooling down and then declined, TG continued to. cooling down, after SHR rats TC, HDL and LDL-C-C rise when cooling, cooling down, after, TG continued to decline.
(3) Results of CA
DA level in A, B and C groups of Wistar rats and SHR rats had significant difference (P<0.05) during the experiment; DA, NE and AD of Wistar rats were elevated in temperature cooling down and dropped down later, however, the temperature were higher than cooling before. The DA of SHR rats lowered when cooling and raise after cooling, and the NE and AD continued to decline.
(4) Results of Mb, cTnl and ET-1
cTnl and ET-1in A, B and C groups of Wistar rats and ET-1in A, B and C groups of SHR rats had the significant difference (P<0.05) during the whole simulation process. Mb, cTnl and ET-1of Wistar rats kept continue to rise and Mb, cTnl and ET-1of SHR rats declined when cooling and raise when the temperature picked up during the whole simulation process, but Mb and ET-1were still lower than before.
3. Conclusions
(1) The cold air activities have the influence on sensitive indexes of CVD in health people and patients, and have the more effect on CVD patients than healthy people.
(2) Cold air meteorological factors is not only one of the direct causes to CVD, but also as a kind of cause leading to unbalance secretion and metabolism of secretion in the body which lead to CVD occurrence, development and the death.
(3) According to the experimental results of the animal and the crowd, DA and ET-1levels in the crowd and animals all changed significantly and had the same change trend, Suggests that the special weather conditions which made by the cold air will have a significant impact on DA and ET llevel。
(4) The same index had the different change trend in two kinds of experiments, this imply us that the results of the animal experiments could not be directly extrapolated to humans.
(5) By the analysis of trend and degree changes of the index, A preliminary judgment of the mechanism we had got were the emergency response of adrenal medulla and vascular endothelin system.
(6) The same index had some different change trend in two kinds of experiments, this imply us that the results of the animal experiments could not be directly extrapolated to humans.
1.人群实验结果
按照研究对象的遴选标准,最终确定病例30例,对照组40例,病例和对照的性别和年龄构成均无显著性差异(P>0.05)。
(1)血脂检测结果
病例组和对照组血脂7项在冷空气过境过程中变化无显著性差异(P>0.05)。在冷空气活动过程中,病例组的TC和LDL-C持续升高,HDL-C先降低后有所升高；对照组TC也持续升高,但LDL-C和HDL-C在过境时升高,过境后下降。上述各指标在冷空气前中后的变化均无显著性差异。
(2)儿茶酚胺检测结果
冷空气过境前、中、后三个时段病例组和对照组的DA水平均有显著差异(P<0.05),NE和AD水平无显著性差异(P>0.05)；在冷空气过程中,病例组DA水平持续下降,NE和AD水平呈持续上升趋势,而对照组的三项指标在冷空气过境时升高,过境后降低。
(3)心肌和血管蛋白检测结果
病例组的Mb、cTnI和ET-1水平以及对照组的Mb和ET-1水平在冷空气过境前、中、后三个阶段其变化均存在显著性差异(P<0.05)；冷空气过程中,病例组和对照组的Mb和cTnI均持续升高,但两组的ET-1则在冷空气过境时升高,过境后降低,且明显低于过境前。
(4)血液流变学检测结果
冷空气过境时,病例组和对照组的全血粘度低切(WBV-L)、中切值(WBV-M)、全血还原粘度低切(WBDV-L)、红细胞聚集指数(AI)和刚性指数(RI)均显著升高(P<0.05),除此之外,病例组全血还原粘度高切值(WBDV-H)和红细胞电泳指数(EI)也显著升高(P<0.05)。
2.动物实验结果
按照动物实验的伦理学要求,在人群现场研究时的实际气温变化基础上,将温度整体上调12.1℃,保持降温的幅度保持不变,作为动物实验的模拟气象条件。
(1)心率和血压检测结果
在冷空气模拟过程中,Wistar大鼠和SHR大鼠的心率先升高后降低,Wistar大鼠B组与A组比较差异显著(P<0.05),与此同时,Wistar大鼠的血压持续升高；SHR大鼠的血压先降低后略有升高,但仍低于A组,B组和C组与A组比较,血压变化均存在显著性差异(P<0.05)。
(2)血脂检测结果
Wistar大鼠A、B、C三组TG水平差异显著(P<0.05),C组明显低于A组和B组(P<0.05),SHR鼠的HDL-C(?)LDL-CB组明显高于A组和C组(P<0.05)；实验过程中,Wistar大鼠TC、TG和HDL-C均呈现持续降低趋势,而LDL-C则在降温时升高,降温后降低；SHR大鼠TC、HDL-C(?)LDL-C在降温时升高,降温后降低,TG则持续下降。
(3)儿茶酚胺类检测结果
进入冷空气模型后,Wistar大鼠和SHR大鼠A、B、C三组的DA水平差异显著(P<0.05); Wistar大鼠组的DA、NE和AD在降温时升高,降温后降低,但仍高于降温前；SHR大鼠DA在降温时降低,降温后升高,但低于降温前,NE和AD则持续下降。
(4)动物实验Mb、cTnl和ET-1检测结果
进入冷空气模型后,Wistar大鼠A、B、C三组的cTnl和ET-1水平差异显著(P<0.05),SHR大鼠A、B、C三组的ET-1差异显著(P<0.05)。实验过程中,Wistar大鼠Mb、cTnI和ET-1持续升高,SHR大鼠Mb、cTn和ET-1在降温时降低,温度回升时升高,但Mb和ET-1仍然低于降温前。
3.结论
(1)冷空气活动过程中,研究对象的血脂、儿茶酚胺、心肌蛋白和血管内皮素及血液流变学等反映心脑血管疾病发生、发展及严重程度的各指标均有变化、提示冷空气活动对对血管、心肌和心脏等心血管系统的影响是多层次、多途径的综合性影响。
(2)冷空气活动对病例组和对照组的影响程度不同,对心脑血管病人的影响比健康人群的影响更大。
(3)冷空气等气象因素不但是导致心脑血管疾病发生发展的直接病因之一,还作为诱因引发体内相关生理指标的分泌和代谢,从而导致疾病发生或出现不同结局。
(4)人群现场调查和动物实验结果均显示,冷空气过程所反映的特殊气象条件能引起机体DA和ET-1水平的显著变化,提示DA和ET-1是冷空气活动对心脑血管疾病影响最为敏感的指标。
(5)通过研究对象各指标的变化程度和趋势分析,初步认为冷空气活动影响心脑血管疾病的机制有：肾上腺髓质系统和血管内皮素应急机制。
(6)人群和动物在个别指标上有些许不同,提示由于种属的不同,将冷空气活动对动物实验的某些结果直接外推到人,还有待充分的论证,结论外推还得谨慎。
Cardio-vascular disease (CVD) has became the first cause of death and one of the serious worldwide public health problem, is also a great threat to the residents'health and social development of our country in recent years. So, exploring the risk factors, occurrence, deterioration and reducing morbidity and mortality of the CVD are the mutual interesting topic in medicine and related interdisciplinary filed in the21st century. A large number of studies have shown that the cold air activity is not only one of the causes of CVD, but also the main inducing cause of CVD acute attacks. With the global climate changes, the cold air affected area is expanding, the frequency of air activities is increasing, and the influence on the health of human been is aggravating, meanwhile, people have adapted to the warm winter and have weak adaptability to cold, the cold air activities will cause more serious hazards and influences to human. According to the reasons above, researching the relationship between cold air activities and CVD, will help to better predict and prevent of occurrence, development and accident of CVD in advance. However, the recent researches on the effects which cold air activities led to CVD were mostly based on the analysis of patients'epidemiological data, It has not been reported or rarely to detect the sensitive indicators of CVD, lacking of quantitative analyze of the effects, effective degree, and the influence mechanism of air condition related CVD as well the dramatic changes of main meteorological factors. For this purpose, two aspects research were carried out below:(1) The city of Zhangye of Gansu province was chosen as a good air quality but more likely affected area by cold air, then the Sensitive indicators associated closely with VCD, such as blood lipid, CA, Mb, cTn I, ET-1, hemorheology were detected before, during and after the cold air transit respectively.(2) The parallel test cold air process as the population was simulated in artificial climate box, and the variation of hart rate, Systolic pressure, diastolic blood pressure, blood lipid, CA, Mb, cTn I and ET-1of the Wistar rats and SHR rats were detected as the same as the crowd, from the data above, to analysis of the influence of cold air activity on CVD sensitive index and explore the possible mechanisms of occurrence, development and dead end, This will provide the basis for prevention, treatment and medical meteorological prediction on CVD care. The main results as follows:
1. Results of field trial
30cases and40controls were bring into the research according to the experimental demand, and tow groups had no significant difference (P>0.05) in gender and age.
(1) Blood lipid test results
Seven items of blood lipid index of Cases and controls had no significant difference during the whole cold air process. And TC and LDL-C continue to rise and HDL-C to decline in the process of cold air activity. TC in the control group continue to rise and LDL and HDL-C lift in the cold air activity then fall after cold air activity. And the changes had no significant difference (P>0.05).
(2) Results of CA
The DA of cases and controls had notable changes before, during and after the cold air activity, statistics test had significant difference (P<0.05) while NE and AD had not. In the whole process, DA level continued to decline, NE and AD kept a trend of rising, while the control group of three indicators is elevated during the activity and reduction after the cold air activity.
(3) Results of Mb, cTnI and ET-1
The Mb, cTnI and ET-1of cases group and the Mb and ET-1of control group had notable changes (P<0.05) before, during and after the cold air activity; Mb and cTnI of case group and the control group continued to rise in the process of cold air transit and the ET-1rise first and then decline to a low level even low than before.
(4) Results of hemorheology
During the cold air activity, the Whole Blood Viscosity (low, middle shear rate), Whole Blood Deoxidize Viscosity (low shear rate), Assembling Index (AI) and Rigidity index (RI) levels of cases and controls increased significantly (P<0.05), and the Whole Blood Deoxidize Viscosity High shear rate (WBDV-H) and Electrophoresis Index (El) raised and the same time..
2. The results of animal experimental
According with the requirements for the ethics of animal experiments, based on the basis of field trail studies, kept the change tendency after lifting12.1℃as animal experiments simulated meteorological conditions.
(1) Test results of the heart rate and blood pressure
During the simulation, the heart rate of SHR and Wistar rats increased when the temperature drop down, and then slowed down with the temperature gradually returned to normal. The blood pressure of Wistar rats groups kept rising, but no significant difference compared with basic values, and the blood pressure of SHR rats groups speed up first then slow down, there were significant differences (P<0.05).
(2) Blood lipid test results
There were significant differences (P<0.05) between TG of A, B, C of Wistar rat group, and the TG of group C was lower than that in group A and group B (P<0.05), The HDL and LDL-C of SHR rats in group B was significantly higher in group A and group C (P<0.05); in the Experiments, TC, TG and HDL-C of Wistar rats kept a trend of decrease, while the LDL-C increase when the temperature reduce and decrease after the drop, The TC, HDL-C and LDL-C of SHR rats rised when temperature cooling down and then declined, TG continued to. cooling down, after SHR rats TC, HDL and LDL-C-C rise when cooling, cooling down, after, TG continued to decline.
(3) Results of CA
DA level in A, B and C groups of Wistar rats and SHR rats had significant difference (P<0.05) during the experiment; DA, NE and AD of Wistar rats were elevated in temperature cooling down and dropped down later, however, the temperature were higher than cooling before. The DA of SHR rats lowered when cooling and raise after cooling, and the NE and AD continued to decline.
(4) Results of Mb, cTnl and ET-1
cTnl and ET-1in A, B and C groups of Wistar rats and ET-1in A, B and C groups of SHR rats had the significant difference (P<0.05) during the whole simulation process. Mb, cTnl and ET-1of Wistar rats kept continue to rise and Mb, cTnl and ET-1of SHR rats declined when cooling and raise when the temperature picked up during the whole simulation process, but Mb and ET-1were still lower than before.
3. Conclusions
(1) The cold air activities have the influence on sensitive indexes of CVD in health people and patients, and have the more effect on CVD patients than healthy people.
(2) Cold air meteorological factors is not only one of the direct causes to CVD, but also as a kind of cause leading to unbalance secretion and metabolism of secretion in the body which lead to CVD occurrence, development and the death.
(3) According to the experimental results of the animal and the crowd, DA and ET-1levels in the crowd and animals all changed significantly and had the same change trend, Suggests that the special weather conditions which made by the cold air will have a significant impact on DA and ET llevel。
(4) The same index had the different change trend in two kinds of experiments, this imply us that the results of the animal experiments could not be directly extrapolated to humans.
(5) By the analysis of trend and degree changes of the index, A preliminary judgment of the mechanism we had got were the emergency response of adrenal medulla and vascular endothelin system.
(6) The same index had some different change trend in two kinds of experiments, this imply us that the results of the animal experiments could not be directly extrapolated to humans.
引文
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