【作者】 朱爱华；

【导师】 田金洲；

【作者基本信息】 北京中医药大学 ， 中医内科学， 2007， 博士

【摘要】 研究目的：血瘀证集中表现在一些血栓相关性疾病中，包括心脑血管疾病、外周动脉闭塞症、深静脉血栓等。在急性脑血管疾病中，炎症反应细胞因子相互调控，参与了脑血管病急症期的血液循环、血管的病理变化过程。我们假定炎症反应还参与了血瘀证的形成。调查急性脑梗塞患者和无脑梗塞对照组人口学因素、外周血的血液理化、血液生化、凝血相关指标、炎症反应因子与急性脑梗塞和急性脑梗塞血瘀证的相关性，从而探讨血瘀证形成的生物学基础。研究方法：研究采用随机对照观察的方法，以急性脑梗塞患者为研究对象，并设立无脑梗塞对照组。收集全部病例的临床一般资料、血液理化、生化、凝血指标等资料；对全部病例进行中医临床辨证分析；每例病例抽取空腹静脉血3ml，用促凝管收集、立即离心超净工作台分离血清，-70℃保存，统一检测，所有过程均严格执行无菌操作，患者采血前均无感染及应用免疫佐剂或免疫抑制剂，采用酶联免疫吸附(ELISA)双夹心抗体法检测血清IL-1β、IL-6、TNF-α、TGF-β、sICAM-1、sVCAM-1含量，试剂盒购自北京环亚泰克生物医学技术有限公司，实验过程在北京中医药大学东直门医院药理实验室完成测定，所有操作均按说明书要求进行。将所收集的资料集中收集录入数据库，通过SPSS10.0统计软件进行统计分析。结果：年龄为人口学因素资料，将病例按年龄＜70岁、年龄≥70岁分为两组，这时，年龄＜70岁组血瘀证35例，非血瘀证组32例；年龄≥70岁组血瘀证44例，非血瘀证19例，经Pearson卡方检验，P＜0.05，两者比较有显著差异。血瘀证分值与年龄相关分析，Pearson相关性系数为0.185，P＜0.05，血瘀证的分值随年龄的增加而增加。凝血酶原时间为血管性危险因素，血瘀证组与非血瘀证组之间凝血酶原时间分别为血瘀证组：12.16±0.95(秒)，非血瘀证组：12.52±1.03(秒)，t检验结果为：P＜0.05，血瘀证组凝血酶原时间缩短。通过对炎症反应因子含量进行分析：在血瘀证组内血瘀证分值与IL-1β水平的Pearson相关系数为0.354，P＜0.01，Spearman等级相关系数为0.305，P＜0.05，血瘀分值与IL-1β水平呈正相关。TNF-α水平与血瘀证的Pearson相关系数为-0.253，P＜0.05，Spearman等级相关相关系数为-0.264，P＜0.01，TNF-α水平与急性脑梗塞血瘀证Spearman等级相关系数为-0.254，P＜0.05，TNF-α水平与血瘀分值呈负相关。TGF-β1水平与急性脑梗塞血瘀证Pearson相关系数为-0.235，P＜0.05，TGF-β1水平与血瘀分值呈负相关。sICAM-1水平与急性脑梗塞血瘀证Spearman等级相关系数为0.342，P＜0.05，急性脑梗塞血瘀证与sICAM-1水平呈正相关。结论：通过对急性脑梗塞组与对照组血瘀证、非血瘀证病例所收集的人口学资料、血管性危险因素如血液理化资料、血脂水平、血液凝集相关指标的相互比较，发现血瘀证相关的因素有年龄；可能与血瘀证相关的因素为凝血酶原时间；而以往所关注的血瘀证相关的因素诸如白细胞计数、血清D-二聚体含量是急性脑梗塞的相关因素。炎症反应因子IL-1β、IL-6、TNF-α、sICAM-1、sVCAM-1参与了急性脑梗塞的炎症反应过程，这些因子的异常升高与急性脑梗塞相关，TGF-β1升高与急性脑梗塞有相关趋势。IL-1β水平与血瘀证呈正相关；sICAM-1水平与急性脑梗塞血瘀证呈正相关；TNF-α水平与血瘀证呈负相关；TGF-β1水平与急性脑梗塞血瘀证呈负相关。炎症反应因子IL-1β、TNF-α、TGB-β1、sICAM-1可能为急性脑梗塞血瘀证的生物学基础，作为一种重要的中医病理过程-血瘀证，除与炎症反应因子IL-1β、TNF-α、TGB-β1、sICAM-1相关外，还有诸如年龄、凝血酶原时间等其他相关因素，血瘀证有可能是通过复杂的机制而完成其发生、发展、形成的过程，在探讨其发生发展形成时应尽可能的将所有影响因素都纳入研究内容，才有可能阐述其形成机制(本课题由国家重点基础研究发展计划973项目(2003CB517104)资助)。更多还原

【Abstract】 BACKGROUND: Blood stasis syndrome usually occurs in diseases related to thrombussuch as cerebrovascular disease, cardiovascular disease, peripheryphlebothrombosis or arterial occlusions. Inflammatory reaction participate theacute cerebrovascular diseases course. These inflammatory cell factorparticipate the procedure of the acute cerebrovascular diseases. So we presumethat inflammatory reaction may be correlated to the emergence of blood stasissyndrome.OBJECTIVE: Analyzing the age, blood pressure, blood examination, blood fat,inflammatory reaction cell factors between the cerebral infarction group andthe control group. Survey the relationship between these targets and the cerebralinfarction. To analyze blood stasis syndrome in both the cerebral infarctiongroup and the control group that without cerebral infarction was conducted toexplore the correlation between inflammatory factor and blood stasis syndrome.METHODS: This subject is an observatory and controlled study based on patientswith cerebral infarction and without cerebral infarction. All these participantswere hospitalized at the Dongzhimen hospital which was the first affiliatedhospital of Beijing University of Traditional Chinese Medicine. We collectedthe name, age, sex, and other information from each participant, including bloodexamination, blood fat and index of blood coagulation and so on. We usequestionnaire to evaluate each participant’s pattern identification. We alsodraw vein blood 3ml from each participant at the state of empty stomach for makingsera. All sera were hold in the-70 centi-degree refrigerator and were detectedtogether in pharmacological laboratory in Dongzhimen hospital. IL-1β、IL-6、TNF-α、TGF-β、sICAM-1 and sVCAM-1 were detected with the enzyme linkedimmunosorbent assay(ELISA) kit of IL-1、IL-6、TNF-α、TGF-β、sICAM-1 and sVCAM-1by the method of ELISA. At last, we finished our database and statisticalanalysis.RESULTS: Age, as an demography information, is very important in this subject.We divided all participants into two groups. 70 years old is selected to be thedemarcation. In the group that with the participants in age＜70 years old, thereare 35 patients with blood stasis syndrome and 32 patients without blood stasissyndrome. In the group that with the participants in age≥70 years old, thereare 44 patients with blood stasis syndrome and 19 patients without blood stasissyndrome. Through Pearson chi-square criterion, we get the result P＜0.05. Thecorrelation test shows that Pearson coefficient correlation between age andblood stasis syndrome score is 0.185, P＜0.05, accompany with the increase ofage, the blood stasis syndrome score is increased. PT is an blood vessel Riskfactor. The PT level in patients with blood stasis syndrome is 12.16±0.95(s).The PT level in patients without blood stasis syndrome is 12.52±1.03(s). t test result shows P＜0.05. Patients with blood stasis syndrome have high PT levelcompare with the patients without blood stasis syndrome. Analyzing theinflammatory factor, the Pearson coefficient correlation between IL-1βleveland the blood stasis syndrome score is 0.354, P＜0.01. Spearman coefficientcorrelation is 0.305, P＜0.05. The result shows the positive correlation betweenIL-1βand blood stasis syndrome. The Pearson coefficient correlation betweenTNF-αlevel and the blood stasis syndrome score is -0.253, P＜0.05. Spearmancoefficient correlation is -0.264, P＜0.01. As the same, The Pearson coefficientcorrelation between TGF-β1 level and the blood stasis syndrome score is -0.235,P＜0.05. The result shows inverse correlation between TNF-αlevel/TGF-β1 leveland the blood stasis syndrome score. The Spearman coefficient correlationbetween sICAM-1 level and the blood stasis syndrome score is 0.342, P＜0.05. Thereis a relationship of positive correlation between sICAM-1 and blood stasissyndrome in cerebral infarction too.CONCLUSION: The correlation factor of blood stasis syndrome is age. The possiblecorrelation factors of blood stasis syndrome are prothrombin time. Inflammatoryfactors IL-1β、IL-6、TNF-α、TGF-β、sICAM-1、sVCAM-1 are participate the cerebralinfarction course. The result shows the positive correlation between IL-1βandblood stasis syndrome. It shows inverse correlation between TNF-αlevel/TGF-β1 level and the blood stasis syndrome score too. Also there is a relationshipof positive correlation between sICAM-1 and blood stasis syndrome in cerebralinfarction. Inflammatory factor participate the cerebral infarction course. Andshow the different correlation with the blood stasis syndrome. Inflammatoryfactors as a biological factor maybe take part in the forming course of bloodstasis syndrome in patients with cerebral infarction. Blood stasis syndrome asan important pattern, may have more complicated mechanism in the course of happen,develop and form. (The project was supported by National 973 programe)更多还原