一、一种半胱氨酸改造的MLIF类似物对大鼠脑缺血再灌注损伤的保护作用的研究 二、兰州地区健康成人脉冲振荡肺功能正常值的分
发布时间：2018-07-29 15:50
【摘要】：研究背景缺血性脑血管病(ischemic cerebrovascular disease,ICVD)是目前在临床上常见的一种神经系统疾病。ICVD发生时,缺血再灌注引起的继发性损伤的关键环节是急性炎症反应。此时细胞因子被大量的释放、粘附分子的表达明显升高,白细胞及其它免疫细胞被激活,从而释放各种炎性介质如细胞因子包括TNF-α、IL-1β、IL-6、IL-8、趋化因子及粘附分子等,TNF-α被认为是炎症网络中的关键因子,是全身炎症反应的始动介质,同时,缺血再灌注时脂质过氧化反应明显加速,自由基的平衡被打破,其产生过量而清除减少,这些因素都严重损伤了神经细胞。因此,减轻炎症反应、减少自由基就对保护缺血再灌注后的神经功能具有重要意义。单核细胞移动抑制因子(monocyte locomotion inhibitory factor,MLIF)是一种抗炎性反应的多肽,它能抑制人单核细胞、多形核白细胞的移动,抑制炎症反应的发生、逃避宿主免疫,同时它还对细胞因子TNF-α、IL-1β等的分泌以及相应受体的表达有明显的抑制作用,从而影响炎症反应的整个过程。研究表明MLIF的抗炎活性基团是Cys-Asn-Ser。本实验试图通过对MLIF的活性基团Cys-Asn-Ser的N端进行修饰,了解新的修饰后的MLIF类似物对大鼠脑缺血再灌注后神经功能改变及TNF-α、IL-1β表达的影响,来研究这种新的MLIF类似物可能的药理作用机制,从而为临床水平的研究提供理论依据,以便将来更好地造福缺血性脑病的患者。目的本实验共分为两个部分,第一部分对抗炎肽MLIF的活性肽段Cys-Asn-Ser的N端进行了全新设计和化学结构改造。为了提高Cys-Asn-Ser的抗氧化活性,我们在Cys-Asn-Ser的N端连接一个极性不带电荷的半胱氨酸。采用固相合成法合成一条全新设计的MLIF类似物Cys-Cys-Asn-Ser以及MLIF活性基团小分子肽段Cys-Asn-Ser。第二部分建立大鼠局灶性脑缺血再灌注损伤模型,以MLIF活性基团小分子肽段Cys-Asn-Ser作为对照,考察这个新的MLIF类似物对大鼠缺血性脑病是否具有治疗作用,并初步探讨这种作用可能的发生机制。方法1.本研究第一部分的化学合成实验中,采用固相合成法,合成一个新的半胱氨酸改造的MLIF类似物Cys-Cys-Asn-Ser和MLIF的活性基团小分子肽段Cys-Asn-Ser,然后对合成的粗肽进行脱盐处理选用的是sephadexg10凝胶柱,并结合制备型hplc纯化粗肽,最后采用ms对纯化产物进行鉴定。2.本研究尝试用线栓来阻塞大脑中动脉,从而构建SD大鼠脑缺血再灌注损伤的模型,待造模成功、缺血再灌注24h的时候,采用Longa法对大鼠神经功能缺损进行评分;大鼠脑切片进行TTC染色,观察脑缺血再灌注后脑梗死体积的变化,探讨这个新的半胱氨酸改造的MLIF类似物Cys-Cys-Asn-Ser对缺血性脑病的治疗作用。3.本研究第二部分动物实验中,在大鼠脑缺血再灌注24h后,取大鼠脑组织匀浆测定TNF-α和il-1β的含量,观察这个新改造的MLIF类似物Cys-Cys-Asn-Ser的抗炎活性。结果1.本研究第一部分的化学合成实验中,采用固相合成法获取的新的由半胱氨酸改造的MLIF类似物Cys-Cys-Asn-Ser和MLIF的活性基团小分子肽段Cys-Asn-Ser,前者的产率是40.5%,后者的产率是61.2%,hplc分离纯化后,证明二者的纯度均达到95%以上,且经质谱对产物的鉴定,结构完全相符。2.本研究第二部分动物实验的结果表明,模型组大鼠均出现了严重的神经功能受损的症状,神经功能评分的结果为(2.20±0.45);大鼠缺血侧的脑组织有非常明显的梗死灶,测得梗死体积为(152.85±28.83)mm3;而与模型组大鼠不同的是,各药物治疗组均在不同程度上改善了MCAO大鼠的病理改变,包括减小脑梗死的体积和降低神经功能评分。与活性基团小分子肽段Cys-Asn-Ser相比,新的MLIF类似物Cys-Cys-Asn-Ser的活性有所提高。3.本实验从TNF-α和il-1β的检测数据来看,用一个半胱氨酸对MLIF活性基团小分子肽段Cys-Asn-Ser修饰后,新的MLIF类似物Cys-Cys-Asn-Ser的抗炎活性有所增强。由此可见,新的MLIF类似物Cys-Cys-Asn-Ser有抑制炎症反应的作用,同时它自身又有着抗氧化的作用,这两方面的原因使得它对于缺血性脑损伤有保护作用。结论一种新的MLIF类似物Cys-Cys-Asn-Ser对缺血性再灌注脑损伤有一定的神经保护作用,同时其修饰后的抗炎活性比MLIF活性基团小分子肽段Cys-Asn-Ser有所增强。背景和研究目的呼吸系统疾病是严重危害人民健康的常见病、多发病,已经构成影响公共健康的重大问题。其不仅发病率高,许多疾病起病隐袭,肺功能损害严重,致残率高,给社会和国民经济造成了巨大损失。因此,呼吸系统疾病的早诊断、早治疗、早预防就显得尤为重要。在呼吸系统疾病的检查方法中,呼吸功能的测定已经越来越受到人们的重视,但肺功能检查常规项目的信号源均是受试者自己的呼吸,检查结果可靠与否与受试者自己的理解能力和配合能力密切相关,对于一些特殊人群如年老、体弱、幼儿等患者,就不能进行这样的检查,而脉冲振荡法(impulse oscillometry,IOS)测定技术的突出优点是受试者仅需平静呼吸,操作简便、适用对象广泛,目前在临床上越来越受到青睐。影响肺功能检查的正常值的因素非常多,主要与受试者的种族、年龄、性别、体重、身高等因素密切相关,其次还与受试者的生存环境、工种、体力活动及吸烟与否等因素也有关。因此,临床上选取合适的预计值,才是提高诊断准确率的关键。中国目前仍然没有统一的脉冲振荡法(IOS)测定的各参数的参考预计值及正常值公式,现在临床沿用的还是欧美国家(主要是欧洲)提供的正常值范围,这些预计值不一定符合中国人的实际,而且国内各地区在应用IOS法做肺功能测定时的标准亦不一致,这样就不利于对疾病做出准确诊断。因此,建立我国自己的IOS肺功能预计值公式显得尤为重要。兰州地处中国西北部地区,由于特殊的地理位置和工业城市的特点,制定出我们兰州地区IOS正常值及预计值公式势在必行。我们的结果将为兰州地区乃至西北五省的临床医生尤其是呼吸科医生提供一个参考,也将为国内其他地区的临床医生提供一个线索,为争取早日建立我国自己的、统一的预计值公式及正常值标准奠定基础。材料和方法研究对象共计920例,其中女470例,男450例。选择对象是(1)2008年2月至2011年12月在兰州大学第二医院进行体检的18岁及以上的健康成人;(2)外科非心肺和非气道疾病择期手术的术前检查者。研究方法欧洲呼吸学会(ERS)推荐的IOS测量标准是本研究所采用的检查方法。检查前至少24 h内未用过胆碱能受体拮抗剂、抗过敏类药物、茶碱类药物、β2受体激动剂、肾上腺素能受体抑制剂及激素类药物等。测定的指标包括:IOS参数、结构参数图、频谱分析图、阻抗容积图(Z-V图)等。其中实验测定的IOS的主要参数为:呼吸总阻抗(Zrs)、中心气道阻力(R_20)、总气道阻力(R_5)、中心阻力(Rc)、周边阻力(Rp)、周边粘性阻力(R_5-R_20)、共振频率(Fres)及周边弹性阻力(X_5)。统计学分析使用SPSS 17.0软件进行数据分析。结果1.对兰州地区920例18岁及以上健康成人严格按照欧洲呼吸学会(RES)推荐的IOS测量标准进行IOS测定,IOS参数Zrs、Fres、R_5、R_20、X_5、Rc、Rp均不呈正态分布。2.各参数正常参考值范围与目前临床上一直在采用的国外提供的正常参考值范围,二者的配对t检验(P0.001)有显著性差异。3.在兰州地区,分别建立了当地成人健康男性和健康女性IOS主要参数(Zrs、Fres、R_5、R_20、X_5、)的正常参考值预计公式。4.共振频率(Fres)均值及95%可信区间均大于目前国内外采用的10Hz正常值,甚至大于15Hz,男女相比无显著性差异。5.根据建立的兰州地区健康成人的IOS各参数的正常参考值预计公式,表明粘性阻力(R)主要与体重、身高相关,与体重呈正相关,而身高的影响最大,呈负相关。6.在本研究所涉及的年龄范围内(18岁~80岁),IOS各参数值(除外X_5)随着年龄的增长无明显变化,而X_5与年龄成负相关。结论兰州地区健康成人脉冲振荡(IOS)肺功能各参数的正常参考值范围及预计值公式与国内、外均有差异,建议中国构建适合国人自己的IOS各参数的正常参考值范围及预计值公式。
[Abstract]:Background ischemic cerebrovascular disease (ischemic cerebrovascular disease, ICVD) is a common clinically common nervous system disease.ICVD. The key link of secondary injury caused by ischemia-reperfusion is acute inflammatory reaction. At this time, the cytokines are released, the expression of adhesion molecules is significantly increased, white blood cells are increased. And other immune cells are activated to release various inflammatory mediators such as cytokines including TNF- alpha, IL-1 beta, IL-6, IL-8, chemokines and adhesion molecules. TNF- is considered to be the key factor in the inflammatory network and is the starting medium of systemic inflammatory reaction. At the same time, the lipid peroxidation obviously accelerates and the free radical is flat at the time of ischemia-reperfusion. Monocyte locomotion inhibitory factor (MLIF) is a polypeptide of anti-inflammatory response. It inhibits the movement of mononuclear cells and polymorphonuclear leukocytes, inhibits the occurrence of inflammatory reactions and escaping host immunity, and it also inhibits the secretion of cytokines TNF- a, IL-1 beta, and the expression of corresponding receptors, thus affecting the whole process of the inflammatory reaction. The study shows that the anti inflammatory active group of MLIF is Cys-Asn-Ser. By modifying the N end of the active group Cys-Asn-Ser of MLIF, this experiment is to understand the effect of the new modified MLIF analogue on the nerve function changes and the expression of TNF- alpha and IL-1 beta after cerebral ischemia reperfusion in rats, to study the possible pharmacological mechanism of this new MLIF analogue, so as to provide a theoretical basis for the study of clinical level. The purpose of this experiment is to be divided into two parts. The first part of this experiment is divided into two parts. The first part is a new design and chemical structure modification against the N terminal of the active peptide Cys-Asn-Ser of the peptide MLIF. In order to improve the antioxidant activity of Cys-Asn-Ser, we connect a polar uncharged at the N end of Cys-Asn-Ser. Cysteine. A new designed MLIF analogue Cys-Cys-Asn-Ser and MLIF active group small molecular peptide Cys-Asn-Ser. second were synthesized by solid phase synthesis, and the focal cerebral ischemia reperfusion injury model was established in rats. The small molecular peptide Cys-Asn-Ser of the MLIF active group was used as the control, and the new MLIF analogue was investigated. Whether the ischemic encephalopathy of rat has a therapeutic effect, and preliminarily discuss the possible mechanism of this effect. Method 1. the first part of the study, in the first part of the chemical synthesis experiment, the solid phase synthesis method was used to synthesize a new cysteine modified MLIF analogue, Cys-Cys-Asn-Ser and MLIF, the small molecule peptide Cys-Asn-Ser of the active group, and then the synthesis was made. The crude peptide is used for desalination, which is sephadexg10 gel column, combined with prepared HPLC to purify the crude peptide, and finally uses MS to identify the purified product. This study attempts to block the middle cerebral artery with a thread to construct a model of cerebral ischemia reperfusion injury in SD rats. The model is successful. When 24h is reperfusion, Longa is used in Longa. The method was used to score the nerve function defect in rats. The rat brain slices were stained with TTC to observe the changes of cerebral infarction volume after cerebral ischemia-reperfusion. The effect of this new MLIF analogue of cysteine on the treatment of ischemic encephalopathy was discussed in the second part of the study, after the cerebral ischemia and reperfusion of 24h in the rat, the rats were treated with 24h. The content of TNF- alpha and IL-1 beta in the rat brain homogenate was measured and the anti-inflammatory activity of the newly transformed MLIF analogue, Cys-Cys-Asn-Ser was observed. Results 1. the first part of the study was a chemical synthesis of a new MLIF analogue of cysteine, Cys-Cys-Asn-Ser and MLIF, obtained by solid phase synthesis. Peptide Cys-Asn-Ser, the yield of the former was 40.5%, the yield of the latter was 61.2%. After HPLC isolation and purification, the purity of the two were all above 95%. And the structure of the product was identified by mass spectrometry. The structure of the second part of the animal experiment in the second part of the study showed that the rats in the model group had serious neurological impairment symptoms. The result of the functional score was (2.20 + 0.45); the cerebral tissue of the ischemic side of the rat had a very obvious infarct and the infarct volume was (152.85 + 28.83) mm3, but different from the model group, the pathological changes of the MCAO rats were improved to varying degrees, including the reduction of the volume of cerebral infarction and the reduction of the neurological function score. Compared with the small molecule peptide segment Cys-Asn-Ser of the active group, the activity of the new MLIF analogue Cys-Cys-Asn-Ser has been improved in.3. experiment, from the detection data of TNF- alpha and IL-1 beta, the anti-inflammatory activity of the new MLIF analogue Cys-Cys-Asn-Ser is enhanced by the modification of the small molecule peptide Cys-Asn-Ser of the MLIF active group with one cysteine. It can be seen that the new MLIF analogue, Cys-Cys-Asn-Ser, has the effect of inhibiting the inflammatory reaction and has its own antioxidant effect. These two reasons make it protective for ischemic brain damage. Conclusion a new MLIF analogue, Cys-Cys-Asn-Ser, has a certain neuroprotective effect on ischemic reperfusion brain injury. Its modified anti-inflammatory activity is stronger than the small molecular peptide segment Cys-Asn-Ser of the MLIF active group. Background and research objective respiratory disease is a common disease which seriously endangers the health of the people. It has become a major problem in the public health. It has been a major problem affecting public health. It not only has high incidence, many diseases are hidden, lung function damage is serious, and the rate of disability. As a result, the early diagnosis, early treatment and early prevention of respiratory system diseases are particularly important. In the examination methods of respiratory system diseases, the measurement of respiratory function has been paid more and more attention, but the signal sources of the routine lung function examination are their own breathing. Whether the results are reliable or not is closely related to the ability to understand and cooperate with the subjects themselves. For some special people, such as old age, body, and young children, it is impossible to carry out such examination, and the protruding advantage of the impulse oscillometry (IOS) measurement technique is that the subjects only need calm breathing, and the operation is simple and applicable. Many factors affecting the normal value of the lung function test are closely related to the race, age, sex, weight and height of the subjects, and the following factors are also related to the living environment, work, physical activity and smoking or not. The estimated value is the key to improving the accuracy of the diagnosis. There is still no reference expected value and normal value formula of the parameters measured by the unified pulse oscillation method (IOS). Now it is still in use in the European and American countries (mainly Europe), which are not necessarily in accordance with the Chinese reality, but also in China. The criteria for the determination of lung function by the IOS method in each area are also inconsistent, which is not conducive to the accurate diagnosis of the disease. Therefore, it is very important to establish the formula of the predicted value of the lung function of our own IOS. Lanzhou is located in the northwest of China, and the special geographical position and the characteristics of the industrial city have made us Lanzhou. The normal value and the predicted value formula of the regional IOS are imperative. Our results will provide a reference for clinicians in the five provinces of Lanzhou and the northwest, especially the Department of respiration doctors, and also provide a clue for the clinicians in other parts of the country to strive for the early establishment of our own, unified predicted value formula and normal value standard. The materials and methods were studied in 920 cases, including 470 women and 450 men. (1) healthy adults aged 18 and above in Second Hospital Affiliated to Lanzhou University from February 2008 to December 2011; (2) preoperative examiners of elective hand surgery for non cardiopulmonary and non airway diseases. Methods European Respiratory Society (ERS). The recommended IOS measurement standard is the method used in this study. Unused cholinergic receptor antagonists, antiallergic drugs, theophylline, beta 2 receptor agonists, adrenergic receptor inhibitors and hormone drugs, including IOS parameters, structural parameters, spectrum analysis, impedance volume, and so on at least 24 h before examination. The main parameters of the experimental IOS were: total respiratory impedance (Zrs), central airway resistance (R_20), total airway resistance (R_5), central resistance (Rc), peripheral resistance (Rp), peripheral viscous resistance (R_5-R_20), resonance frequency (Fres) and peripheral elastic resistance (X_5). Statistical analysis used SPSS 17 software to carry out data analysis. Results 1. pairs of data. 920 healthy adults aged 18 and over in Lanzhou were determined strictly according to the IOS measurement standard recommended by the European Society of respiratory (RES). IOS parameters Zrs, Fres, R_5, R_20, X_5, Rc, Rp are not normal distribution of the normal reference range of the.2. parameters and the normal range of reference values that are currently being used abroad, and the two P0.001 has significant difference.3. in Lanzhou region, the normal reference value of local adult healthy male and healthy female IOS parameters (Zrs, Fres, R_5, R_20, X_5), the mean value of.4. resonance frequency (Fres) and 95% confidence interval are greater than that of 10Hz normal values, even larger than 15Hz, and no men and women. The significant difference.5. based on the normal reference value prediction formula of the IOS parameters of healthy adults in Lanzhou area, indicating that the viscosity resistance (R) is mainly related to body weight, height and body weight, and the height has the greatest influence, and the negative correlation.6. is within the age range of 18 years (18 years old) and IOS values (except X_5). The growth of age has no significant change, but X_5 is negatively correlated with age. Conclusion the normal reference value range and prediction formula of lung function parameters of healthy adults in Lanzhou region are different from those at home and abroad. It is suggested that China construct the normal reference range and the predicted value formula suitable for the number of IOS of Chinese people.
【学位授予单位】：兰州大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R743.3
本文编号：2153173
[Abstract]:Background ischemic cerebrovascular disease (ischemic cerebrovascular disease, ICVD) is a common clinically common nervous system disease.ICVD. The key link of secondary injury caused by ischemia-reperfusion is acute inflammatory reaction. At this time, the cytokines are released, the expression of adhesion molecules is significantly increased, white blood cells are increased. And other immune cells are activated to release various inflammatory mediators such as cytokines including TNF- alpha, IL-1 beta, IL-6, IL-8, chemokines and adhesion molecules. TNF- is considered to be the key factor in the inflammatory network and is the starting medium of systemic inflammatory reaction. At the same time, the lipid peroxidation obviously accelerates and the free radical is flat at the time of ischemia-reperfusion. Monocyte locomotion inhibitory factor (MLIF) is a polypeptide of anti-inflammatory response. It inhibits the movement of mononuclear cells and polymorphonuclear leukocytes, inhibits the occurrence of inflammatory reactions and escaping host immunity, and it also inhibits the secretion of cytokines TNF- a, IL-1 beta, and the expression of corresponding receptors, thus affecting the whole process of the inflammatory reaction. The study shows that the anti inflammatory active group of MLIF is Cys-Asn-Ser. By modifying the N end of the active group Cys-Asn-Ser of MLIF, this experiment is to understand the effect of the new modified MLIF analogue on the nerve function changes and the expression of TNF- alpha and IL-1 beta after cerebral ischemia reperfusion in rats, to study the possible pharmacological mechanism of this new MLIF analogue, so as to provide a theoretical basis for the study of clinical level. The purpose of this experiment is to be divided into two parts. The first part of this experiment is divided into two parts. The first part is a new design and chemical structure modification against the N terminal of the active peptide Cys-Asn-Ser of the peptide MLIF. In order to improve the antioxidant activity of Cys-Asn-Ser, we connect a polar uncharged at the N end of Cys-Asn-Ser. Cysteine. A new designed MLIF analogue Cys-Cys-Asn-Ser and MLIF active group small molecular peptide Cys-Asn-Ser. second were synthesized by solid phase synthesis, and the focal cerebral ischemia reperfusion injury model was established in rats. The small molecular peptide Cys-Asn-Ser of the MLIF active group was used as the control, and the new MLIF analogue was investigated. Whether the ischemic encephalopathy of rat has a therapeutic effect, and preliminarily discuss the possible mechanism of this effect. Method 1. the first part of the study, in the first part of the chemical synthesis experiment, the solid phase synthesis method was used to synthesize a new cysteine modified MLIF analogue, Cys-Cys-Asn-Ser and MLIF, the small molecule peptide Cys-Asn-Ser of the active group, and then the synthesis was made. The crude peptide is used for desalination, which is sephadexg10 gel column, combined with prepared HPLC to purify the crude peptide, and finally uses MS to identify the purified product. This study attempts to block the middle cerebral artery with a thread to construct a model of cerebral ischemia reperfusion injury in SD rats. The model is successful. When 24h is reperfusion, Longa is used in Longa. The method was used to score the nerve function defect in rats. The rat brain slices were stained with TTC to observe the changes of cerebral infarction volume after cerebral ischemia-reperfusion. The effect of this new MLIF analogue of cysteine on the treatment of ischemic encephalopathy was discussed in the second part of the study, after the cerebral ischemia and reperfusion of 24h in the rat, the rats were treated with 24h. The content of TNF- alpha and IL-1 beta in the rat brain homogenate was measured and the anti-inflammatory activity of the newly transformed MLIF analogue, Cys-Cys-Asn-Ser was observed. Results 1. the first part of the study was a chemical synthesis of a new MLIF analogue of cysteine, Cys-Cys-Asn-Ser and MLIF, obtained by solid phase synthesis. Peptide Cys-Asn-Ser, the yield of the former was 40.5%, the yield of the latter was 61.2%. After HPLC isolation and purification, the purity of the two were all above 95%. And the structure of the product was identified by mass spectrometry. The structure of the second part of the animal experiment in the second part of the study showed that the rats in the model group had serious neurological impairment symptoms. The result of the functional score was (2.20 + 0.45); the cerebral tissue of the ischemic side of the rat had a very obvious infarct and the infarct volume was (152.85 + 28.83) mm3, but different from the model group, the pathological changes of the MCAO rats were improved to varying degrees, including the reduction of the volume of cerebral infarction and the reduction of the neurological function score. Compared with the small molecule peptide segment Cys-Asn-Ser of the active group, the activity of the new MLIF analogue Cys-Cys-Asn-Ser has been improved in.3. experiment, from the detection data of TNF- alpha and IL-1 beta, the anti-inflammatory activity of the new MLIF analogue Cys-Cys-Asn-Ser is enhanced by the modification of the small molecule peptide Cys-Asn-Ser of the MLIF active group with one cysteine. It can be seen that the new MLIF analogue, Cys-Cys-Asn-Ser, has the effect of inhibiting the inflammatory reaction and has its own antioxidant effect. These two reasons make it protective for ischemic brain damage. Conclusion a new MLIF analogue, Cys-Cys-Asn-Ser, has a certain neuroprotective effect on ischemic reperfusion brain injury. Its modified anti-inflammatory activity is stronger than the small molecular peptide segment Cys-Asn-Ser of the MLIF active group. Background and research objective respiratory disease is a common disease which seriously endangers the health of the people. It has become a major problem in the public health. It has been a major problem affecting public health. It not only has high incidence, many diseases are hidden, lung function damage is serious, and the rate of disability. As a result, the early diagnosis, early treatment and early prevention of respiratory system diseases are particularly important. In the examination methods of respiratory system diseases, the measurement of respiratory function has been paid more and more attention, but the signal sources of the routine lung function examination are their own breathing. Whether the results are reliable or not is closely related to the ability to understand and cooperate with the subjects themselves. For some special people, such as old age, body, and young children, it is impossible to carry out such examination, and the protruding advantage of the impulse oscillometry (IOS) measurement technique is that the subjects only need calm breathing, and the operation is simple and applicable. Many factors affecting the normal value of the lung function test are closely related to the race, age, sex, weight and height of the subjects, and the following factors are also related to the living environment, work, physical activity and smoking or not. The estimated value is the key to improving the accuracy of the diagnosis. There is still no reference expected value and normal value formula of the parameters measured by the unified pulse oscillation method (IOS). Now it is still in use in the European and American countries (mainly Europe), which are not necessarily in accordance with the Chinese reality, but also in China. The criteria for the determination of lung function by the IOS method in each area are also inconsistent, which is not conducive to the accurate diagnosis of the disease. Therefore, it is very important to establish the formula of the predicted value of the lung function of our own IOS. Lanzhou is located in the northwest of China, and the special geographical position and the characteristics of the industrial city have made us Lanzhou. The normal value and the predicted value formula of the regional IOS are imperative. Our results will provide a reference for clinicians in the five provinces of Lanzhou and the northwest, especially the Department of respiration doctors, and also provide a clue for the clinicians in other parts of the country to strive for the early establishment of our own, unified predicted value formula and normal value standard. The materials and methods were studied in 920 cases, including 470 women and 450 men. (1) healthy adults aged 18 and above in Second Hospital Affiliated to Lanzhou University from February 2008 to December 2011; (2) preoperative examiners of elective hand surgery for non cardiopulmonary and non airway diseases. Methods European Respiratory Society (ERS). The recommended IOS measurement standard is the method used in this study. Unused cholinergic receptor antagonists, antiallergic drugs, theophylline, beta 2 receptor agonists, adrenergic receptor inhibitors and hormone drugs, including IOS parameters, structural parameters, spectrum analysis, impedance volume, and so on at least 24 h before examination. The main parameters of the experimental IOS were: total respiratory impedance (Zrs), central airway resistance (R_20), total airway resistance (R_5), central resistance (Rc), peripheral resistance (Rp), peripheral viscous resistance (R_5-R_20), resonance frequency (Fres) and peripheral elastic resistance (X_5). Statistical analysis used SPSS 17 software to carry out data analysis. Results 1. pairs of data. 920 healthy adults aged 18 and over in Lanzhou were determined strictly according to the IOS measurement standard recommended by the European Society of respiratory (RES). IOS parameters Zrs, Fres, R_5, R_20, X_5, Rc, Rp are not normal distribution of the normal reference range of the.2. parameters and the normal range of reference values that are currently being used abroad, and the two P0.001 has significant difference.3. in Lanzhou region, the normal reference value of local adult healthy male and healthy female IOS parameters (Zrs, Fres, R_5, R_20, X_5), the mean value of.4. resonance frequency (Fres) and 95% confidence interval are greater than that of 10Hz normal values, even larger than 15Hz, and no men and women. The significant difference.5. based on the normal reference value prediction formula of the IOS parameters of healthy adults in Lanzhou area, indicating that the viscosity resistance (R) is mainly related to body weight, height and body weight, and the height has the greatest influence, and the negative correlation.6. is within the age range of 18 years (18 years old) and IOS values (except X_5). The growth of age has no significant change, but X_5 is negatively correlated with age. Conclusion the normal reference value range and prediction formula of lung function parameters of healthy adults in Lanzhou region are different from those at home and abroad. It is suggested that China construct the normal reference range and the predicted value formula suitable for the number of IOS of Chinese people.
【学位授予单位】：兰州大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R743.3
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