肿瘤、糖尿病、高血压、冠心病等复杂性疾病血栓前状态的中、维、西医研究
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摘要
目的
肿瘤、糖尿病、高血压、冠心病等复杂性疾病是多基因病,此已成为危害人类健康的最大杀手。是现代生物学的研究热点之一。近年来,科研人员在当代医学研究的主流工作上引入系统复杂性理论,即整体大于局部之和,从整体的角度研究系统,探索生命现象与疾病的本质。研究发现,肿瘤、糖尿病、高血压、冠心病等复杂性疾病虽然在诊断和治疗方案等方面都是各异的,但都有用现代医学病理生理的共同机理,如神经内分泌免疫网络紊乱及血栓前状态改变等。关于肿瘤、糖尿病、高血压、冠心病等复杂性疾病血栓前状态指标改变的国内外研究越来越多,但是都局限于单一疾病某些指标的研究上,而对多个复杂性疾病同时进行多个血栓前状态指标变化检测的报道甚少。
面对肿瘤、糖尿病、高血压、冠心病等疾病的复杂现象,中医、维吾尔医学各有独特认识和理论。痰瘀、异常黑胆质作为中医和维吾尔医学中常见的致病因素或病理产物,与肿瘤、糖尿病、高血压、冠心病等复杂性疾病的发生密切相关。
本课题把多个复杂性疾病作为一个整体,从血栓前状态指标(血小板表面膜糖蛋白CD41(Claster of differentioation 41,CD41)、P.选择素(P-selectin,CD62p);组织型纤溶酶原激活物(plasma tissue plasminogen activator,t-PA)和组织型纤溶酶原激活物抑制剂(plasma tissue plasminogen activator inhibitor,PAI-1);内皮素(endothelin,ET-1);凝血四项:包括纤维蛋白原(fibrinogen,FIB)、活化部分凝血活酶时间(activated partial thromboplastin time,APTT)、凝血酶时间(thrombin time,TT)及凝血酶原时间(prothrombin time,PT))入手,探讨肿瘤、糖尿病、高血压、冠心病等复杂性疾病血栓前状态改变的共性机制及系统疾病性。并以中医、维吾尔医学理论为指导,探求复杂性疾中医病痰瘀证,复杂性疾病维医异常黑胆质证的血栓前状态;寻找三种医学在肿瘤、糖尿病、高血压、冠心病等复杂性疾病血栓前状态等方面的交互性,为全面了解肿瘤、糖尿病、高血压、冠心病等复杂性疾病的发生发展过程和新的治疗方法寻求新的思路。
方法
病例来源为2006年2月至2006年6月在新疆医科大学附属医院住院的肿瘤、糖尿病、高血压和冠心病患者共285例,进行西医的诊断分型,并按中医、维吾尔医的方法进行辨证分型。正常对照组33例,为经体检无心、肺、肝、肾及血液等疾病的健康人。对所有研究对象进行以下方面的测定:用流式细胞术测定患者血小板表面CD41,cI)62p;用放射免疫法检测血清ET-1;用ELISA方法检测血浆t-PA, PAI.1;全自动血凝分析仪检测凝血四项即血浆纤维蛋白原(FIB)水平、活化部分凝血活酶时间(APTT)、凝血酶原时问(PT)、凝血酶时间(TT)。动物实验:1)分别采用二磷酸腺苷(ADP)、胶原诱导兔血小板聚集,测定血小板的最大聚集率: 2)建立大鼠动一静脉旁路血栓形成模型,测定血栓湿重;3)放射免疫法测定血浆TXB2和6-kET-lo-PGFla的含量;4)采用玻片法测定体外凝血时间。统计学方法:所有实验数据采用SPSS13.0统计软件处理,用均数士标准差(x±s)表示:采用单因素方差分析,两组间比较采用t检验,P<0.05有统计学意义。
结果
1.复杂性疾病血栓前状态的研究
1.1肿瘤患者血栓前状态的研究
肿瘤组CD62P、PAl-1、FIB、ET-1三项指标均较正常组增高(P<0.05),肿瘤组t-PA水平较正常组降低(P<0.05);肿瘤组APTT、PT时间明显缩短(P<0.05):血小板表面CD41的表达及TT时间与正常组比较无显著性差异(P>0.05);
1.2糖尿病患者血栓前状态的研究
糖尿病组血小板表面CD62P的表达、血浆PAI-1、FIB三项指标均较正常组增高(P <0.05),而t-PA水平较正常组降低(P<0.05);糖尿病组APTT、PT时间时间明显缩短(P<0.05);糖尿病组血小板表面CD41的表达,血清ET-1水平及TT时间与正常组比较无显著性差异(P>0.05);糖尿病伴血管病变组血小板表面CD62P的表达、血浆PAI-1、FIB三项指标均较不伴血管病变组增高(P<0.05);糖尿病伴血管病变组活化部分凝血活酶时间(APTT)及凝血酶时间(TT)较不伴血管病变组明显缩短(P<0.05);糖尿病伴血管病变组序小板表面CD41的表达、血浆t-PA水平、血清ET-1水平及凝血酶原时间(PT)与不伴血管病变组指标比较没有显著性差异(P>0.05);
1.3高血压患者血栓前状态的研究
高血压组血小板表面CD62P的表达、血浆PAI-1、FIB三项指标均较正常组增高(P <0.05),而t-PA水平较正常组降低(P<0.05);高血压APTT、PT时间时间明显缩短(P<0.05);高血压组血小板表面CD41的表达,血清ET-1水平及TT时间与正常组比较无显著性差异(P>0.05);
1.4冠心病患者血栓前状态的研究
冠心病组血小板表面CD62P的表达、血浆PAI-1、FIB三项指标均较正常组增高(P <0.05),而t-PA水平较正常组降低(P<0.05);冠心病组APTT时间明显缩短(P<0.05);冠心病组血小板表面CD41的表达,血清ET-1水平、PT及TT时间与正常组比较无显著性差异(P>0.05);
1.5肿瘤、糖尿病、高血压、冠心病等复杂性疾病血栓前状态改变的共性
与正常对照组比较,各疾病组血小板表面CD62p的表达及血浆PAI-1水平明显升高(P<0.05);与正常对照组比较各疾病组血浆t-PA的含量明显降低(P<0.05);与正常对照组比较肿瘤组血清ET-1水平明显升高(P<0.05),而其他疾病组与正常对照组血清ET-1水平改变不明显(P>0.05);与正常对照组比较,各疾病组.APTT时间明显缩短(P<0.05);与正常对照组比较各疾病组血浆FIB浓度明显升高(P< 0.05),其中肿瘤组血浆:FIB浓度的变化比其三个他疾病组更为明显;与正常对照组比较肿瘤组、糖尿病组及高血压组PT时间明显缩短(P<0.05);上述指标进行疾病组间比较差异无显著性(P>0.05)。
2.肿瘤、糖尿病、高血压、冠心病等复杂性疾病中医分型及其血栓前状态的研究
2.1肿瘤、糖尿病、高血压、冠心病等复杂性疾病中痰瘀证所占比例为76.84%,非痰瘀证组占23.16%,痰瘀证所占比例远远大于非痰瘀证;而痰瘀证型中痰证占26.03%、瘀证占19.63%,痰瘀交阻证占54.34%,超过一半以上。
2.2
1)与对照组比较,复杂性疾病痰瘀证组血小板CD41及血清ET-1无差异(P >0.05),血小板CD62P有统计学意义(P<0.01)(其中痰瘀交阻证>瘀证>痰证>与非痰瘀证>对照组),t-PA含量下降(P<0.05)(其中痰瘀交阻证<瘀证<痰证<非痰瘀证<对照组),PAI.1含量升高(P<0.01)(其中痰瘀交阻证>瘀证>痰证>非痰瘀证>对照组),FIB含量升高(P<0.01)(其中痰瘀交阻证>瘀证>痰证>与非痰瘀证>对照组),PT、APTT时间均缩短(P<0.01)(其中对照组>非痰瘀证>痰证>瘀证>痰瘀交阻证组),TT则无统计学差异(P>0.05);
2)与非痰瘀证组对比,痰瘀证组CD62P阳性百分数明显增多(P<0.01)(其中瘀证组P<0.05,痰瘀交阻证组P<0.01),Fib含量亦显著升高(P<0.01)(其中瘀证组P<0.05,痰瘀交阻证组P<0.01)。而CD41阳性百分数、t-PA及PAI-1含量、PT、TT和APTT则无统计学差异(P>0.05),但各指标在痰证、瘀证、痰瘀交阻证以及非痰瘀证组,并且以痰瘀交阻证组变化最为明显。3.肿瘤、糖尿病、高血压、冠心病等复杂性疾病维医分型及其血栓前状态的研究
3.1在复杂性疾病285例患者中,属异常黑胆质证的有188例,非异常黑胆质证为97例;异常黑胆质证占全部病例的65.96%,非异常黑胆质证占34.04%,异常黑胆质证所占比例大于非异常黑胆质证。
3.2与正常对照组相比,异常黑胆质证组CD62p、FIB、PA.I、ET_l水平均升高(尸<0.01);t-PA水平降低(P<0.05);PT、APTT时间明显缩短(P<0.05),而CD41、1vr的差异不显著(P>0.05).
3.3与正常对照组相比,复杂性疾病异常黑胆质证型和非异常黑胆质证型患者ET-1水平均明显升高(P<0.05)。异常黑胆质证ET-1水平高于异常血液质证组和异常胆液质证组(P<0.05)。且ET-1水平在各组间呈:异常黑胆质证组>异常胆液质证组>异常粘液质证组>异常血液质证组>对照组;与正常对照组相比,复杂性疾病异常黑胆质证型和非异常黑胆质证型患者CD41阳性表达率无明显差异(P>0.05): (;D62P阳性表达率均明显升高(P<0.05)。异常黑胆质证CD62P水平高于异常血液质证组和异常胆液质证组(P<0.05)。且CD62P阳性表达率在各组间呈:异常黑胆质证组>异常血液质证组>异常粘液质证组>异常胆液质证组>对照组;与正常对照组相比,复杂性疾病异常黑胆质证型和非异常黑胆质证型患者t-PA含量均下降(P<0.05);PAI-1含量均升高(P<0.05)。且t-PA含量在各组间呈:异常黑胆质证组<异常粘液质证组<异常胆液质证组<异常血液质证组<对照组;PAI-1含量在各组间呈:异常黑胆质证组>异常粘液质证组>异常胆液质证组>异常血液质证组>;与正常对照组相比,复杂性疾病异常黑胆质证型和非异常黑胆质证型患者FIB含量明显升高(P<0.05),PT、APTT时间明显缩短(P<0.05),而TT的差异不显著(P>0.05)。异常黑胆质证FIB含量高于异常血液质证组和异常粘液质证组(P <0.05)。在凝血四项指标检测结果中,PT、FIB和APTT都有不同程度的变化,PT、APTT时间长短依次为异常黑胆质证组>异常粘液质证组>异常血液质证组>异常胆液质证组>对照组;FIB含量依次异常黑胆质证组>异常粘液质证组>异常胆液质证组>异常血液质证组>对照组。
4.肿瘤、糖尿病、高血压、冠心病等复杂性疾病中医痰瘀证与维医异常黑胆质证血栓前状态的对比研究
4.1与正常对照组相比,痰瘀证组和异常黑胆质证组CD62p、FIB、:PAI-1水平均升高(P<0.01),但二者之间无显著性差异(P>0.05);两组t-PA水平均降低(P <0.05),但两组间比较无差异(P>0.05);两组ET-1均升高(P<0.05),二者之间亦无差异(P>0.05);两组CD4l水平均下降,但差异无统计学意义(P>0.05)。
4.2与正常对照组相比,ET-1、CD62p、FIB、PAl水平在异常黑胆质证组和非异常黑胆质证组均升高(P<0.05),以异常黑胆质证组升高明显,但异常黑胆质证组与非异常黑胆质证组相比,上述指标差异无统计学意义(P>0.05);。t-PA水平在异常黑胆质证患者组和非异常黑胆质证组均下降(P<0.05),以异常黑胆质证组下降更明显,但与非异常黑胆质证组相比无明显差异(P>0.05)。CD41在各组间比较差异均无统计学意义(P>0.05)。
结论
1.肿瘤、糖尿病、高血压、冠心病等复杂性疾病具有血栓前状态改变的共性。血栓前状态的改变可能是肿瘤、糖尿病、高血压、冠心病等复杂性疾病共存的病生基础之一。结合其神经内分泌免疫网络紊乱特点,可推测肿瘤、糖尿病、高血压、冠心病等复杂性疾病具有疾病系统性,即肿瘤、糖尿病、高血压、冠心病等复杂性疾病不仅仅是某一器官和脏器的病变,而是机体全身性的变化。
2.痰瘀证可能是肿瘤、糖尿病、高血压、冠心病等复杂性疾病的中医重要证型。与复杂性疾病非痰瘀证患者相比,复杂性疾病痰瘀证患者血栓前状态改变更明显,尤其是CD62p、t-PA、PAI-1、PT、Fib、APTT改变为主。由此,建议将血栓前状态相关指标纳入量化判断复杂性疾病中医痰瘀证之中。
3.异常黑胆质证可能是复杂性疾病维吾尔医重要证型。与复杂性疾病非异常黑胆质证患者相比复杂性疾病异常黑胆质证的患者血栓前状态改变更明显,尤其是CD62p、t-PA、PAI-1、PT、Fib、APTT改变为主,由此,建议将血栓前状态相关指标也纳入到量化判断复杂性疾病维医异常黑胆质证之中。
4.中医痰瘀证与维医异常黑胆质证在复杂性疾病中的重要证型性、高龄性、血栓前状态改变更加明显性等方面是交互的。我们推测中医痰瘀证与维医异常黑胆质证可能是肿瘤、糖尿病、高血压、冠心病等复杂性疾病的同一病生状态在不同医学的阐述。
5.血管内皮细胞损伤、血小板活化、血液粘度增高、纤溶功能降低是形成血栓的原因,而这一过程可能是体内气机、气化失常,津液代谢障碍形成痰瘀证的过程,亦可能是异常体液堆积、“燃烧”最终产生异常黑胆质证的过程。由此可见,血栓前状态可能是痰瘀与异常黑胆质产生的共同物质基础之一;另外血栓、痰瘀、异常黑胆质三者相似,它们既是病理产物,又可能是致病因素。
6.复杂性疾病非痰瘀证与非异常黑胆质证患者同样存在血栓前状态,但程度较痰瘀证和异常黑胆质证型患者为弱,从微观辨证方面分析,可以推测复杂性疾病非痰瘀证和非异常黑胆质证患者虽然没有痰瘀证和异常黑胆质证的临床宏观表现,但血栓前状态等微观指标的异常提示肿瘤、糖尿病、高血压和冠心病等复杂性疾病患者可能处于痰瘀证和异常黑胆质证的“前状态”,伴随着疾病的发展,复杂性疾病非痰瘀证和复杂性疾病非异常黑胆质证患者可能出现痰瘀证和异常黑胆质证的宏观临床表现。此方面的研究正在进行。
7.中医认为“久病入络”、“久病必瘀”、“怪病多痰”、“痰生百病”;维医理论有“病久必黑(异常黑胆质)”、“病重有黑(异常黑胆质)”之说。肿瘤、糖尿病、高血压、冠心病等复杂性疾病中痰瘀证、异常黑胆质证为多见,我们可否认为,痰瘀证或异常黑胆质证是肿瘤、糖尿病、高血压、冠心病等复杂性疾病的较严重阶段。为此,我们可否本着“既病防变”的原则,在肿瘤、糖尿病、高血压、冠心病等复杂性疾病治疗中结合现代医学的治疗方法,尽早合用中医活血化瘀、化痰补虚法或\和维医异常黑胆质成熟、清除疗法,并以血栓前状态相关指标作为观察对象,以提高肿瘤、糖尿病、高血压、冠心病等复杂性疾病的疗效。此方面的研究已成为我们另一研究方向。
Objective
Complex Diseases such as malignant cancer, cardiovascular diseases and diabetes, caused by the common interaction of multiple genes and environmental factors, are threatening human beings. In recent years scientists put forward anew way of studying the human body as one whole system. Being inspired by the new thinking, we found it extremely necessary to find out the pathogenesis and mechanism of the complex diseases from the Whole Theory point of view. This step is important in order to provide a new treatment method. It has been discovered that cancer, diabetes, hypertension and cardiovascular diseases have many differences on their diagnosis' and treatments, however all of these have pathophysiological change, prethrombotic state (PTS) in common. PTS includes the changes of vascular endothelial cells, platelets, blood clotting and anti blood clotting system. So far the relationship between PTS and complex diseases has been studied by many scientists all over the world, but only restricted to one or two types of diseases or one or two types of PTS indexes. In this research we put four types of complex diseases together, they were considered to be a unit which made the same changes in the body, we tried to prove this theory by checking the PTS indexes. We are hoping this might help us improve the diagnosis and treatment of complex diseases.
Chinese traditional and Uyghur medicines always stress the importance of considering the human body as a whole unit. They also emphasize that when treating diseases we should also pay attention to improving the quality of every organ in the body. These two medicines have their own unique theories and treatment methods for complex diseases.
Phlegm-blood stasis and Abnormal Savda are two different products and pathological risk factors in the human body. They can create the most serious conditions. The diseases that are related to them include cancer, hypertension, coronorey heart disease, diabetes, etc, In this study we assumed that PTS might be one of the common pathological mechanisms of complex diseases in Western, Chinese and Uyghur Medicines. We intended to find out the specific changes of PTS in complex diseases both in Western and Chinese (Uyghur) Medicine, by using this method we tried to discover the commonalities in both medicines to provide an even more effective treatment method for complex diseases.
Methods
69 cases of malignant cancer, 92 cases of diabetes, 68 cases of hypertension, and 55 cases of coronary heart diseases were provided by the Affiliated Hospital of Xinjiang Medical University. Patients were classified according to Chinese Traditional and Uygur Medicine fluid theory. For the control group, 33 cases of healthy individuals were checked to make sure they did not have hypertension, diabetes or other heart, liver, kidney and blood diseases. The expression of CD41, CD62p on platelets, the level of plasma tissue plasminogen activator (t-PA) and its inhibiter (PAI-1), the level of endothelin (ET-1), Activated partial thromboplastin time (APTT), Fibrinogen (FIB), Prothrombin time (PT) and Thrombin time (TT) were tested by using Flow Cytometer, ELISA method, radioimmunoassay method and auto coagulometer. Statistical analysis:SPSS13.0 was used in the study. The data was expressed as means±standard deviation (SD). Statistical significance of a comparison was determined by using ANOVA. The difference between means was considered to be statistically significant if P<0.05.
Results
1. Complex diseases and the prethrombotic state
1.1 Prethrombotic State and the Cancer Patients:Compared to the control group, the average amount of CD62P, the level of plasma FIB, plasma PAI-1 and serum ET-1 in the tumor group were increased (P<0.05). The level of t-PA in the tumor group was decreased compared to the control group (P<0.05); APTT, PT were significantly shorter in the tumor group (P<0.05); there were no significant changes in the amount of platelet CD41 and TT in both groups.
1.2 Prethrombotic State and the Diabetes Mellitus:Compared to the control group, the average amount of CD62P, the level of plasma FIB and plasma PAI-1 in the diabetes group were increased (P<0.05); the level of t-PA in the diabetes group was decreased compared to the control group; APTT, PT and TT were significantly shorter in the diabetes group; the group with angiopathy had a significant increase in the amount of platelet CD62P, the level of plasma PAI-1 and FIB compared to the group without angiopathy (P<0.05); the APTT and TT in the group with angiopathy were significantly shorter than the group without angiopathy (P<0.05); between these two groups there was no significant difference in the plasma t-PA level and PT (P>0.05).
1.3 Prethrombotic State and the hypertension:Compared to the control group, the average amount of CD62P, the level of plasma FIB and PAI-1 in the hypertension group were increased (P<0.05); the level of t-PA in the hypertension group was decreased compared to the control group (P<0.05); APTT, PT and TT were significantly shorter in the hypertension group (P<0.05); there were no significant changes in the amoount of platelet CD41, serum ET-land TT in both groups.
1.4 Prethrombotic State and the coronary heart disease:Compared to the control group, the average amount of CD62P, the level of plasma FIB and PAI-1 in the coronary heart disease group were increased (P<0.05); the level of t-PA in the coronary heart disease group was decreased compared to the control group (P<0.05); APTT was significantly shorter in the coronary heart disease group (P<0.05); there were no significant changes in the amount of platelet CD41, serum ET-1, APTT and TT in both groups.
1.5 Comparative study of cancer, diabetes, hypertension and coronary heart diseases:Compared to the control group, the average amount of CD62P, the level of plasma PAI-1 in the complex disease groups were significantly increased (P<0.05); the level of t-PA in the complex disease groups was decreased; compared to the control group there was a significant increase in the level of serum ET-1 in the tumor group. However, there was no significant difference in the ET-1 level between the control group and the rest of the complex disease groups (P>0.05). There was also no difference in the amount of CD41 between the complex disease groups and the control group (P>0.05); there was no significant difference in the above indexes between the different groups of diseases (P >0.05). Compared to the control group, the APTT was significantly shorter in the complex disease groups (P<0.05). Compared to the control group the level of FIB was significantly increased in the complex disease groups and the change was more obvious in the tumor group (P<0.05). Compared to the control group, PT was significantly shorter in the tumor, diabetes and hypertension groups (P<0.05); there were no significant changes in APTT, PT and TT between the different groups of diseases (P>0.05).
2. The classification of complex diseases in Traditional Chinese Medicine and their relationship to the prethrombotic state
2.1 The proportion of phlegm-stasis syndrome in complex diseases was 76.84%, non-phlegm-stasis syndrome was 23.16%; the proportion of phlegm syndrome in phlegm-stasis syndrome was 24.66%, stasis syndrome was 19.18%, combined phlegm and stasis syndrome was 56.16%.
2.2①Compared to the control group, there was no significant difference in the amount of CD41 and TT in phlegm-stasis syndrome (P>0.05). The amount of CD62p was high (P<0.01) in the phlegm syndrome, stasis syndrome, combined phlegm and stasis syndrome (P<0.01). The levels of t-PA were low (P<0.05) in the phlegm syndrome (P >0.05), stasis syndrome, combined phlegm and stasis syndrome (P<0.05). PAI-1 was high (P<0.05) in the phlegm syndrome, stasis syndrome (P<0.05), combined phlegm and stasis syndrome P<0.01). Fib was high (P<0.01) in the phlegm syndrome, stasis syndrome, combined phlegm and stasis syndrome (P<0.01). PT, APTT was shorter in the phlegm syndrome, stasis syndrome, combined phlegm and stasis syndrome (P<0.01).②Compared to the non-phlegm-stasis syndrome, the amount of CD62p and Fib in the phlegm-stasis syndrome was high (P<0.01) in the phlegm syndrome (P>0.05), stasis syndrome (P<0.05), combined phlegm and stasis syndrome (P<0.01). Although the amount of CD41, t-PA, PAI-1, PT, TT and APTT were insignificantly different between the two syndromes (P>0.05), each item in,the phlegm syndrome, stasis syndrome, combined phlegm and stasis syndrome and non-phlegm-stasis syndrome all presented certain levels of changes. The changes in the combined phlegm and stasis syndrome were very obvious.
3. The classification of complex diseases in Uyghur Medicine and their relations to the Prethrombotic State
3.1 There were 188 cases of Abnormal Savda patients and 97 cases of non Abnormal Savda patients among the 285 cases of complex disease patients. Among the total clinical cases, the ratio of Abnormal Savda patients was 65.95%, the ratio of non Abnormal Savda patients was 34.04%.
3.2 Compared to the control group, the average amount of CD62P, the plasma PAI-1, FIB and serum ET-1 in the Abnormal Savda group were significantly increased (P<0.05). The level of t-PA in the Abnormal Savda group was decreased. There was no difference in the amount of CD41 between the Abnormal Savda group and the control group (P>0.05). Compared to the control group, the APTT and PT were significantly shorter in the Abnormal Savda group (P<0.05); there was no significant change in TT between the two groups (P>0.05).
3.3 Compared to the control group, the level of ET-1 was significantly increased in both the Abnormal Savda and the non Abnormal Savda groups (P<0.05). Compared to the Abnormal Kan and the Abnormal Sapra group, the level of ET-1 was higher in the Abnormal Savda group (P<0.05). The level of ET-1 had various changes among the four fluid groups and the control group, eg:Abnormal Savda>Abnormal Sapra>Abnormal Balham> Abnormal Kan>the control group. Compared to the control group, there was no significant change in the amount of platelet CD41 in the Abnormal Savda and the non Abnormal Savda group (P>0.05). The amount of CD62P was significantly increased (P <0.05). Compared to the Abnormal Kan and the Abnormal Sapra groups, the level of CD62P was higher in the Abnormal Savda group (P<0.05). CD62P had different levels of changes among the four fluid groups and the control group, eg:Abnormal Savda> Abnormal Kan>Abnormal Balham>Abnormal Sapra>the control group. Compared to the control group, the level of plasma t-PA was significantly low in the Abnormal Savda and the non Abnormal Savda group (P<0.05). The level of plasma PAI-1 was increased significantly in these two groups (P<0.05). The level of t-PA varied among the four fluid groups and the control group, eg:Abnormal Savda< Abnormal BalhamAbnormal Balham>Abnormal Sapra> Abnormal Kan>the control group. Compared to the control group, the level of plasma FIB was significantly higher in the Abnormal Savda and the non Abnormal Savda group (P<0.05). PT, APTT were significantly shorter (P<0.05), but there was no difference in TT (P>0.05). Compared to the Abnormal Kan and the Abnormal Balham, the level of FIB was significantly increased (P<0.05). The various changes of PT and APTT were:Abnormal Savda > Abnormal Balham > Abnormal Kan>Abnormal Savda>the control group. The various changes of FIB was Abnormal Savda> Abnormal Balham> Abnormal Savda>Abnormal Kan>the control group; TT had no change among these groups.
4. Comparative Studies of phlegm-stasis syndrome and Abnormal Savda 4.1 Compared to the control group, CD62p, FIB and PAI were significantly increased in patients with Tanyuhuzu Syndrome and the Abnormal Savda Syndrome (P<0.01), but there was no statistical difference between them (P>0.05). These two groups had a lower t-PA level (P<0.05), again with no difference between them (P>0.05). ET-1 was significantly increased in these two groups (P>0.05), again there was no difference between them (P<0.05). The level of CD41 in these three groups didn't show a significant difference.
4.2 Compared to the control group, ET-l,CD62p, FIB and PAI were significantly increased in patients with Abnormal Savda Syndrome and non-Abnormal Savda Syndrome (P<0.05). The increase in the Abnormal Savda Syndrome group was more significant than the non-Abnormal Savda. Both groups had lower t-PA levels (P<0.05), the decrease in the Abnormal Savda Syndrome group was more significant, but when these two groups were compared there was no statistical difference (P>0.05). The level of CD41 in these three groups didn't change.
Conclusion
1. PTS is a common change in complex diseases such as tumors, diabetes, hypertension and coronary heart disease, PTS might be also one of the common pathophysiological basises of complex diseases. As far as the common changes of neuroen-docrine-immune pathway in complex diseases are concerned, it can be concluded that tumors, diabetes, hypertension and coronary heart diseases are systematic diseases. That is to say complex disease is not the only change in a certain organ but the overall change of the body.
2. Phlegm-stasis syndrome might be an important syndrome type of tumors, diabetes, hypertension and coronary heart diseases in Chinese Traditional Medicine. PTS is more obvious in Phlegm-stasis syndrome than that of the non Phlegm-stasis syndrome in complex diseases; especially the changes of CD62p, t-PA, PAI-l,PT,Fib, APTT which are more significant in Phlegm-stasis syndrome. From that result, we might consider applying the PTS indexes to quantitative judgment of Phlegm-stasis syndrome in complex diseases.
3. Abnormal Savda Syndrome might be an important syndrome type in tumors, diabetes, hypertension and coronary heart diseases in Uyghur Medicine. PTS is more obvious in the Abnormal Savda syndrome than that of the non Abnormal Savda syndrome; especially the changes of CD62p,t-PA,PAI-1,PT,Fib, APTT which are more significant in Abnormal Savda Syndrome. From that result, we might consider applying the PTS indexes to a quantitative judgment of Abnormal Savda syndrome in complex diseases.
4. Phlegm-stasis syndrome in Chinese Traditional Medicine and the Abnormal Savda syndrome in Uyghur Medicine are interactive according to their importance as a syndrome; they both happen in older patients and the changes of of PTS indexes are obvious in both. From this interaction we have concluded that the Phlegm-stasis syndrome in Chinese Traditional Medicine and the Abnormal Savda syndrome in Uyghur Medicine might be a pathological state of the same disease in different medical explanations. Is PTS one of the probable material foundations of these two? Are the Phlegm-stasis in Traditional Chinese Medicine and the Abnormal Savda in Uyghur Medicine the direct causes of PTS in complex diseases? It is necessary to study these assumptions further.
5. Vascular endothelial cell injury, platelet activation, increased blood viscosity and reduced fibrinolytic function are the reasons for the formation of blood clot. This process might be a common way for the Phlegm-stasis syndrome which includes Qi, gasification disorders and impaired fluid metabolism. This process also might be the one for the accumulation and burning of Abnormal Savda which eventually leads to the Abormal Savda syndrome. From that result we can assume that, prethromnotic state might be one of the material foundations of Phlegm-stasis and Abnormal Savda. Blood clot, Phlegm-stasis and Abnormal Savda are very similar, they are not only the Pathological products but also the risk factors.
6. Prethromboitic state exists both in the Non Phlegm- statis syndrom and the non Abnornal Savda syndrom in complex diseases, but the level of the prethromboitic state is lower in the Non Phlegm- statis syndrom and the non Abnornal Savda syndrom than that of the Phlegm- statis syndrome and the Abnornal Savda syndrome. Although there is no obvious clinical symptoms of the Phlegm- statis syndrome and the Abnornal Savda syndrome in Non Phlegm- statis syndrom and non Abnornal Savda syndrom in complex diseases, disorders in prethromboitic state indicate that tumors, diabetes, hypertension and coronary heart diseases patients might be in the prestage of the Phlegm- statis syndrome and the Abnornal Savda syndrome. As the diseases progress, there will be clinical manifestations of Phlegm- statis syndrome and Abnornal Savda syndrome in the Non Phlegm- statis syndrom and the non Abnornal Savda syndrome in complex diseases.
7. Traditional Chinese Medicine considers that "the Tongxinluo a long illness", "a long illness goes into the blood", "Abnormal Duo Tan", "Sputum causes all disease"; Uyghur Medicine considers that "black disease after a long time", "black in diseases". Phlegm-stasis syndrome in Chinese Traditional Medicine and Abnormal Savda syndrome in Uyghur Medicine happens a lot among tumors, diabetes, hypertension and coronary heart diseases. From that can we consider using Huo Xue Hua Tan and Hua Tan Bu Xu method in Traditional Chinese Medicine and Munziq and Mushil in Uyghur medicine whenever we encounter any complex diseases? Also pay close attention to the changes of TS indexes in order to increase the treatment effect of complex disease such as tumors, diabetes, hypertension and coronary heart diseases. This research has to be further researched.
肿瘤、糖尿病、高血压、冠心病等复杂性疾病是多基因病,此已成为危害人类健康的最大杀手。是现代生物学的研究热点之一。近年来,科研人员在当代医学研究的主流工作上引入系统复杂性理论,即整体大于局部之和,从整体的角度研究系统,探索生命现象与疾病的本质。研究发现,肿瘤、糖尿病、高血压、冠心病等复杂性疾病虽然在诊断和治疗方案等方面都是各异的,但都有用现代医学病理生理的共同机理,如神经内分泌免疫网络紊乱及血栓前状态改变等。关于肿瘤、糖尿病、高血压、冠心病等复杂性疾病血栓前状态指标改变的国内外研究越来越多,但是都局限于单一疾病某些指标的研究上,而对多个复杂性疾病同时进行多个血栓前状态指标变化检测的报道甚少。
面对肿瘤、糖尿病、高血压、冠心病等疾病的复杂现象,中医、维吾尔医学各有独特认识和理论。痰瘀、异常黑胆质作为中医和维吾尔医学中常见的致病因素或病理产物,与肿瘤、糖尿病、高血压、冠心病等复杂性疾病的发生密切相关。
本课题把多个复杂性疾病作为一个整体,从血栓前状态指标(血小板表面膜糖蛋白CD41(Claster of differentioation 41,CD41)、P.选择素(P-selectin,CD62p);组织型纤溶酶原激活物(plasma tissue plasminogen activator,t-PA)和组织型纤溶酶原激活物抑制剂(plasma tissue plasminogen activator inhibitor,PAI-1);内皮素(endothelin,ET-1);凝血四项:包括纤维蛋白原(fibrinogen,FIB)、活化部分凝血活酶时间(activated partial thromboplastin time,APTT)、凝血酶时间(thrombin time,TT)及凝血酶原时间(prothrombin time,PT))入手,探讨肿瘤、糖尿病、高血压、冠心病等复杂性疾病血栓前状态改变的共性机制及系统疾病性。并以中医、维吾尔医学理论为指导,探求复杂性疾中医病痰瘀证,复杂性疾病维医异常黑胆质证的血栓前状态;寻找三种医学在肿瘤、糖尿病、高血压、冠心病等复杂性疾病血栓前状态等方面的交互性,为全面了解肿瘤、糖尿病、高血压、冠心病等复杂性疾病的发生发展过程和新的治疗方法寻求新的思路。
方法
病例来源为2006年2月至2006年6月在新疆医科大学附属医院住院的肿瘤、糖尿病、高血压和冠心病患者共285例,进行西医的诊断分型,并按中医、维吾尔医的方法进行辨证分型。正常对照组33例,为经体检无心、肺、肝、肾及血液等疾病的健康人。对所有研究对象进行以下方面的测定:用流式细胞术测定患者血小板表面CD41,cI)62p;用放射免疫法检测血清ET-1;用ELISA方法检测血浆t-PA, PAI.1;全自动血凝分析仪检测凝血四项即血浆纤维蛋白原(FIB)水平、活化部分凝血活酶时间(APTT)、凝血酶原时问(PT)、凝血酶时间(TT)。动物实验:1)分别采用二磷酸腺苷(ADP)、胶原诱导兔血小板聚集,测定血小板的最大聚集率: 2)建立大鼠动一静脉旁路血栓形成模型,测定血栓湿重;3)放射免疫法测定血浆TXB2和6-kET-lo-PGFla的含量;4)采用玻片法测定体外凝血时间。统计学方法:所有实验数据采用SPSS13.0统计软件处理,用均数士标准差(x±s)表示:采用单因素方差分析,两组间比较采用t检验,P<0.05有统计学意义。
结果
1.复杂性疾病血栓前状态的研究
1.1肿瘤患者血栓前状态的研究
肿瘤组CD62P、PAl-1、FIB、ET-1三项指标均较正常组增高(P<0.05),肿瘤组t-PA水平较正常组降低(P<0.05);肿瘤组APTT、PT时间明显缩短(P<0.05):血小板表面CD41的表达及TT时间与正常组比较无显著性差异(P>0.05);
1.2糖尿病患者血栓前状态的研究
糖尿病组血小板表面CD62P的表达、血浆PAI-1、FIB三项指标均较正常组增高(P <0.05),而t-PA水平较正常组降低(P<0.05);糖尿病组APTT、PT时间时间明显缩短(P<0.05);糖尿病组血小板表面CD41的表达,血清ET-1水平及TT时间与正常组比较无显著性差异(P>0.05);糖尿病伴血管病变组血小板表面CD62P的表达、血浆PAI-1、FIB三项指标均较不伴血管病变组增高(P<0.05);糖尿病伴血管病变组活化部分凝血活酶时间(APTT)及凝血酶时间(TT)较不伴血管病变组明显缩短(P<0.05);糖尿病伴血管病变组序小板表面CD41的表达、血浆t-PA水平、血清ET-1水平及凝血酶原时间(PT)与不伴血管病变组指标比较没有显著性差异(P>0.05);
1.3高血压患者血栓前状态的研究
高血压组血小板表面CD62P的表达、血浆PAI-1、FIB三项指标均较正常组增高(P <0.05),而t-PA水平较正常组降低(P<0.05);高血压APTT、PT时间时间明显缩短(P<0.05);高血压组血小板表面CD41的表达,血清ET-1水平及TT时间与正常组比较无显著性差异(P>0.05);
1.4冠心病患者血栓前状态的研究
冠心病组血小板表面CD62P的表达、血浆PAI-1、FIB三项指标均较正常组增高(P <0.05),而t-PA水平较正常组降低(P<0.05);冠心病组APTT时间明显缩短(P<0.05);冠心病组血小板表面CD41的表达,血清ET-1水平、PT及TT时间与正常组比较无显著性差异(P>0.05);
1.5肿瘤、糖尿病、高血压、冠心病等复杂性疾病血栓前状态改变的共性
与正常对照组比较,各疾病组血小板表面CD62p的表达及血浆PAI-1水平明显升高(P<0.05);与正常对照组比较各疾病组血浆t-PA的含量明显降低(P<0.05);与正常对照组比较肿瘤组血清ET-1水平明显升高(P<0.05),而其他疾病组与正常对照组血清ET-1水平改变不明显(P>0.05);与正常对照组比较,各疾病组.APTT时间明显缩短(P<0.05);与正常对照组比较各疾病组血浆FIB浓度明显升高(P< 0.05),其中肿瘤组血浆:FIB浓度的变化比其三个他疾病组更为明显;与正常对照组比较肿瘤组、糖尿病组及高血压组PT时间明显缩短(P<0.05);上述指标进行疾病组间比较差异无显著性(P>0.05)。
2.肿瘤、糖尿病、高血压、冠心病等复杂性疾病中医分型及其血栓前状态的研究
2.1肿瘤、糖尿病、高血压、冠心病等复杂性疾病中痰瘀证所占比例为76.84%,非痰瘀证组占23.16%,痰瘀证所占比例远远大于非痰瘀证;而痰瘀证型中痰证占26.03%、瘀证占19.63%,痰瘀交阻证占54.34%,超过一半以上。
2.2
1)与对照组比较,复杂性疾病痰瘀证组血小板CD41及血清ET-1无差异(P >0.05),血小板CD62P有统计学意义(P<0.01)(其中痰瘀交阻证>瘀证>痰证>与非痰瘀证>对照组),t-PA含量下降(P<0.05)(其中痰瘀交阻证<瘀证<痰证<非痰瘀证<对照组),PAI.1含量升高(P<0.01)(其中痰瘀交阻证>瘀证>痰证>非痰瘀证>对照组),FIB含量升高(P<0.01)(其中痰瘀交阻证>瘀证>痰证>与非痰瘀证>对照组),PT、APTT时间均缩短(P<0.01)(其中对照组>非痰瘀证>痰证>瘀证>痰瘀交阻证组),TT则无统计学差异(P>0.05);
2)与非痰瘀证组对比,痰瘀证组CD62P阳性百分数明显增多(P<0.01)(其中瘀证组P<0.05,痰瘀交阻证组P<0.01),Fib含量亦显著升高(P<0.01)(其中瘀证组P<0.05,痰瘀交阻证组P<0.01)。而CD41阳性百分数、t-PA及PAI-1含量、PT、TT和APTT则无统计学差异(P>0.05),但各指标在痰证、瘀证、痰瘀交阻证以及非痰瘀证组,并且以痰瘀交阻证组变化最为明显。3.肿瘤、糖尿病、高血压、冠心病等复杂性疾病维医分型及其血栓前状态的研究
3.1在复杂性疾病285例患者中,属异常黑胆质证的有188例,非异常黑胆质证为97例;异常黑胆质证占全部病例的65.96%,非异常黑胆质证占34.04%,异常黑胆质证所占比例大于非异常黑胆质证。
3.2与正常对照组相比,异常黑胆质证组CD62p、FIB、PA.I、ET_l水平均升高(尸<0.01);t-PA水平降低(P<0.05);PT、APTT时间明显缩短(P<0.05),而CD41、1vr的差异不显著(P>0.05).
3.3与正常对照组相比,复杂性疾病异常黑胆质证型和非异常黑胆质证型患者ET-1水平均明显升高(P<0.05)。异常黑胆质证ET-1水平高于异常血液质证组和异常胆液质证组(P<0.05)。且ET-1水平在各组间呈:异常黑胆质证组>异常胆液质证组>异常粘液质证组>异常血液质证组>对照组;与正常对照组相比,复杂性疾病异常黑胆质证型和非异常黑胆质证型患者CD41阳性表达率无明显差异(P>0.05): (;D62P阳性表达率均明显升高(P<0.05)。异常黑胆质证CD62P水平高于异常血液质证组和异常胆液质证组(P<0.05)。且CD62P阳性表达率在各组间呈:异常黑胆质证组>异常血液质证组>异常粘液质证组>异常胆液质证组>对照组;与正常对照组相比,复杂性疾病异常黑胆质证型和非异常黑胆质证型患者t-PA含量均下降(P<0.05);PAI-1含量均升高(P<0.05)。且t-PA含量在各组间呈:异常黑胆质证组<异常粘液质证组<异常胆液质证组<异常血液质证组<对照组;PAI-1含量在各组间呈:异常黑胆质证组>异常粘液质证组>异常胆液质证组>异常血液质证组>;与正常对照组相比,复杂性疾病异常黑胆质证型和非异常黑胆质证型患者FIB含量明显升高(P<0.05),PT、APTT时间明显缩短(P<0.05),而TT的差异不显著(P>0.05)。异常黑胆质证FIB含量高于异常血液质证组和异常粘液质证组(P <0.05)。在凝血四项指标检测结果中,PT、FIB和APTT都有不同程度的变化,PT、APTT时间长短依次为异常黑胆质证组>异常粘液质证组>异常血液质证组>异常胆液质证组>对照组;FIB含量依次异常黑胆质证组>异常粘液质证组>异常胆液质证组>异常血液质证组>对照组。
4.肿瘤、糖尿病、高血压、冠心病等复杂性疾病中医痰瘀证与维医异常黑胆质证血栓前状态的对比研究
4.1与正常对照组相比,痰瘀证组和异常黑胆质证组CD62p、FIB、:PAI-1水平均升高(P<0.01),但二者之间无显著性差异(P>0.05);两组t-PA水平均降低(P <0.05),但两组间比较无差异(P>0.05);两组ET-1均升高(P<0.05),二者之间亦无差异(P>0.05);两组CD4l水平均下降,但差异无统计学意义(P>0.05)。
4.2与正常对照组相比,ET-1、CD62p、FIB、PAl水平在异常黑胆质证组和非异常黑胆质证组均升高(P<0.05),以异常黑胆质证组升高明显,但异常黑胆质证组与非异常黑胆质证组相比,上述指标差异无统计学意义(P>0.05);。t-PA水平在异常黑胆质证患者组和非异常黑胆质证组均下降(P<0.05),以异常黑胆质证组下降更明显,但与非异常黑胆质证组相比无明显差异(P>0.05)。CD41在各组间比较差异均无统计学意义(P>0.05)。
结论
1.肿瘤、糖尿病、高血压、冠心病等复杂性疾病具有血栓前状态改变的共性。血栓前状态的改变可能是肿瘤、糖尿病、高血压、冠心病等复杂性疾病共存的病生基础之一。结合其神经内分泌免疫网络紊乱特点,可推测肿瘤、糖尿病、高血压、冠心病等复杂性疾病具有疾病系统性,即肿瘤、糖尿病、高血压、冠心病等复杂性疾病不仅仅是某一器官和脏器的病变,而是机体全身性的变化。
2.痰瘀证可能是肿瘤、糖尿病、高血压、冠心病等复杂性疾病的中医重要证型。与复杂性疾病非痰瘀证患者相比,复杂性疾病痰瘀证患者血栓前状态改变更明显,尤其是CD62p、t-PA、PAI-1、PT、Fib、APTT改变为主。由此,建议将血栓前状态相关指标纳入量化判断复杂性疾病中医痰瘀证之中。
3.异常黑胆质证可能是复杂性疾病维吾尔医重要证型。与复杂性疾病非异常黑胆质证患者相比复杂性疾病异常黑胆质证的患者血栓前状态改变更明显,尤其是CD62p、t-PA、PAI-1、PT、Fib、APTT改变为主,由此,建议将血栓前状态相关指标也纳入到量化判断复杂性疾病维医异常黑胆质证之中。
4.中医痰瘀证与维医异常黑胆质证在复杂性疾病中的重要证型性、高龄性、血栓前状态改变更加明显性等方面是交互的。我们推测中医痰瘀证与维医异常黑胆质证可能是肿瘤、糖尿病、高血压、冠心病等复杂性疾病的同一病生状态在不同医学的阐述。
5.血管内皮细胞损伤、血小板活化、血液粘度增高、纤溶功能降低是形成血栓的原因,而这一过程可能是体内气机、气化失常,津液代谢障碍形成痰瘀证的过程,亦可能是异常体液堆积、“燃烧”最终产生异常黑胆质证的过程。由此可见,血栓前状态可能是痰瘀与异常黑胆质产生的共同物质基础之一;另外血栓、痰瘀、异常黑胆质三者相似,它们既是病理产物,又可能是致病因素。
6.复杂性疾病非痰瘀证与非异常黑胆质证患者同样存在血栓前状态,但程度较痰瘀证和异常黑胆质证型患者为弱,从微观辨证方面分析,可以推测复杂性疾病非痰瘀证和非异常黑胆质证患者虽然没有痰瘀证和异常黑胆质证的临床宏观表现,但血栓前状态等微观指标的异常提示肿瘤、糖尿病、高血压和冠心病等复杂性疾病患者可能处于痰瘀证和异常黑胆质证的“前状态”,伴随着疾病的发展,复杂性疾病非痰瘀证和复杂性疾病非异常黑胆质证患者可能出现痰瘀证和异常黑胆质证的宏观临床表现。此方面的研究正在进行。
7.中医认为“久病入络”、“久病必瘀”、“怪病多痰”、“痰生百病”;维医理论有“病久必黑(异常黑胆质)”、“病重有黑(异常黑胆质)”之说。肿瘤、糖尿病、高血压、冠心病等复杂性疾病中痰瘀证、异常黑胆质证为多见,我们可否认为,痰瘀证或异常黑胆质证是肿瘤、糖尿病、高血压、冠心病等复杂性疾病的较严重阶段。为此,我们可否本着“既病防变”的原则,在肿瘤、糖尿病、高血压、冠心病等复杂性疾病治疗中结合现代医学的治疗方法,尽早合用中医活血化瘀、化痰补虚法或\和维医异常黑胆质成熟、清除疗法,并以血栓前状态相关指标作为观察对象,以提高肿瘤、糖尿病、高血压、冠心病等复杂性疾病的疗效。此方面的研究已成为我们另一研究方向。
Objective
Complex Diseases such as malignant cancer, cardiovascular diseases and diabetes, caused by the common interaction of multiple genes and environmental factors, are threatening human beings. In recent years scientists put forward anew way of studying the human body as one whole system. Being inspired by the new thinking, we found it extremely necessary to find out the pathogenesis and mechanism of the complex diseases from the Whole Theory point of view. This step is important in order to provide a new treatment method. It has been discovered that cancer, diabetes, hypertension and cardiovascular diseases have many differences on their diagnosis' and treatments, however all of these have pathophysiological change, prethrombotic state (PTS) in common. PTS includes the changes of vascular endothelial cells, platelets, blood clotting and anti blood clotting system. So far the relationship between PTS and complex diseases has been studied by many scientists all over the world, but only restricted to one or two types of diseases or one or two types of PTS indexes. In this research we put four types of complex diseases together, they were considered to be a unit which made the same changes in the body, we tried to prove this theory by checking the PTS indexes. We are hoping this might help us improve the diagnosis and treatment of complex diseases.
Chinese traditional and Uyghur medicines always stress the importance of considering the human body as a whole unit. They also emphasize that when treating diseases we should also pay attention to improving the quality of every organ in the body. These two medicines have their own unique theories and treatment methods for complex diseases.
Phlegm-blood stasis and Abnormal Savda are two different products and pathological risk factors in the human body. They can create the most serious conditions. The diseases that are related to them include cancer, hypertension, coronorey heart disease, diabetes, etc, In this study we assumed that PTS might be one of the common pathological mechanisms of complex diseases in Western, Chinese and Uyghur Medicines. We intended to find out the specific changes of PTS in complex diseases both in Western and Chinese (Uyghur) Medicine, by using this method we tried to discover the commonalities in both medicines to provide an even more effective treatment method for complex diseases.
Methods
69 cases of malignant cancer, 92 cases of diabetes, 68 cases of hypertension, and 55 cases of coronary heart diseases were provided by the Affiliated Hospital of Xinjiang Medical University. Patients were classified according to Chinese Traditional and Uygur Medicine fluid theory. For the control group, 33 cases of healthy individuals were checked to make sure they did not have hypertension, diabetes or other heart, liver, kidney and blood diseases. The expression of CD41, CD62p on platelets, the level of plasma tissue plasminogen activator (t-PA) and its inhibiter (PAI-1), the level of endothelin (ET-1), Activated partial thromboplastin time (APTT), Fibrinogen (FIB), Prothrombin time (PT) and Thrombin time (TT) were tested by using Flow Cytometer, ELISA method, radioimmunoassay method and auto coagulometer. Statistical analysis:SPSS13.0 was used in the study. The data was expressed as means±standard deviation (SD). Statistical significance of a comparison was determined by using ANOVA. The difference between means was considered to be statistically significant if P<0.05.
Results
1. Complex diseases and the prethrombotic state
1.1 Prethrombotic State and the Cancer Patients:Compared to the control group, the average amount of CD62P, the level of plasma FIB, plasma PAI-1 and serum ET-1 in the tumor group were increased (P<0.05). The level of t-PA in the tumor group was decreased compared to the control group (P<0.05); APTT, PT were significantly shorter in the tumor group (P<0.05); there were no significant changes in the amount of platelet CD41 and TT in both groups.
1.2 Prethrombotic State and the Diabetes Mellitus:Compared to the control group, the average amount of CD62P, the level of plasma FIB and plasma PAI-1 in the diabetes group were increased (P<0.05); the level of t-PA in the diabetes group was decreased compared to the control group; APTT, PT and TT were significantly shorter in the diabetes group; the group with angiopathy had a significant increase in the amount of platelet CD62P, the level of plasma PAI-1 and FIB compared to the group without angiopathy (P<0.05); the APTT and TT in the group with angiopathy were significantly shorter than the group without angiopathy (P<0.05); between these two groups there was no significant difference in the plasma t-PA level and PT (P>0.05).
1.3 Prethrombotic State and the hypertension:Compared to the control group, the average amount of CD62P, the level of plasma FIB and PAI-1 in the hypertension group were increased (P<0.05); the level of t-PA in the hypertension group was decreased compared to the control group (P<0.05); APTT, PT and TT were significantly shorter in the hypertension group (P<0.05); there were no significant changes in the amoount of platelet CD41, serum ET-land TT in both groups.
1.4 Prethrombotic State and the coronary heart disease:Compared to the control group, the average amount of CD62P, the level of plasma FIB and PAI-1 in the coronary heart disease group were increased (P<0.05); the level of t-PA in the coronary heart disease group was decreased compared to the control group (P<0.05); APTT was significantly shorter in the coronary heart disease group (P<0.05); there were no significant changes in the amount of platelet CD41, serum ET-1, APTT and TT in both groups.
1.5 Comparative study of cancer, diabetes, hypertension and coronary heart diseases:Compared to the control group, the average amount of CD62P, the level of plasma PAI-1 in the complex disease groups were significantly increased (P<0.05); the level of t-PA in the complex disease groups was decreased; compared to the control group there was a significant increase in the level of serum ET-1 in the tumor group. However, there was no significant difference in the ET-1 level between the control group and the rest of the complex disease groups (P>0.05). There was also no difference in the amount of CD41 between the complex disease groups and the control group (P>0.05); there was no significant difference in the above indexes between the different groups of diseases (P >0.05). Compared to the control group, the APTT was significantly shorter in the complex disease groups (P<0.05). Compared to the control group the level of FIB was significantly increased in the complex disease groups and the change was more obvious in the tumor group (P<0.05). Compared to the control group, PT was significantly shorter in the tumor, diabetes and hypertension groups (P<0.05); there were no significant changes in APTT, PT and TT between the different groups of diseases (P>0.05).
2. The classification of complex diseases in Traditional Chinese Medicine and their relationship to the prethrombotic state
2.1 The proportion of phlegm-stasis syndrome in complex diseases was 76.84%, non-phlegm-stasis syndrome was 23.16%; the proportion of phlegm syndrome in phlegm-stasis syndrome was 24.66%, stasis syndrome was 19.18%, combined phlegm and stasis syndrome was 56.16%.
2.2①Compared to the control group, there was no significant difference in the amount of CD41 and TT in phlegm-stasis syndrome (P>0.05). The amount of CD62p was high (P<0.01) in the phlegm syndrome, stasis syndrome, combined phlegm and stasis syndrome (P<0.01). The levels of t-PA were low (P<0.05) in the phlegm syndrome (P >0.05), stasis syndrome, combined phlegm and stasis syndrome (P<0.05). PAI-1 was high (P<0.05) in the phlegm syndrome, stasis syndrome (P<0.05), combined phlegm and stasis syndrome P<0.01). Fib was high (P<0.01) in the phlegm syndrome, stasis syndrome, combined phlegm and stasis syndrome (P<0.01). PT, APTT was shorter in the phlegm syndrome, stasis syndrome, combined phlegm and stasis syndrome (P<0.01).②Compared to the non-phlegm-stasis syndrome, the amount of CD62p and Fib in the phlegm-stasis syndrome was high (P<0.01) in the phlegm syndrome (P>0.05), stasis syndrome (P<0.05), combined phlegm and stasis syndrome (P<0.01). Although the amount of CD41, t-PA, PAI-1, PT, TT and APTT were insignificantly different between the two syndromes (P>0.05), each item in,the phlegm syndrome, stasis syndrome, combined phlegm and stasis syndrome and non-phlegm-stasis syndrome all presented certain levels of changes. The changes in the combined phlegm and stasis syndrome were very obvious.
3. The classification of complex diseases in Uyghur Medicine and their relations to the Prethrombotic State
3.1 There were 188 cases of Abnormal Savda patients and 97 cases of non Abnormal Savda patients among the 285 cases of complex disease patients. Among the total clinical cases, the ratio of Abnormal Savda patients was 65.95%, the ratio of non Abnormal Savda patients was 34.04%.
3.2 Compared to the control group, the average amount of CD62P, the plasma PAI-1, FIB and serum ET-1 in the Abnormal Savda group were significantly increased (P<0.05). The level of t-PA in the Abnormal Savda group was decreased. There was no difference in the amount of CD41 between the Abnormal Savda group and the control group (P>0.05). Compared to the control group, the APTT and PT were significantly shorter in the Abnormal Savda group (P<0.05); there was no significant change in TT between the two groups (P>0.05).
3.3 Compared to the control group, the level of ET-1 was significantly increased in both the Abnormal Savda and the non Abnormal Savda groups (P<0.05). Compared to the Abnormal Kan and the Abnormal Sapra group, the level of ET-1 was higher in the Abnormal Savda group (P<0.05). The level of ET-1 had various changes among the four fluid groups and the control group, eg:Abnormal Savda>Abnormal Sapra>Abnormal Balham> Abnormal Kan>the control group. Compared to the control group, there was no significant change in the amount of platelet CD41 in the Abnormal Savda and the non Abnormal Savda group (P>0.05). The amount of CD62P was significantly increased (P <0.05). Compared to the Abnormal Kan and the Abnormal Sapra groups, the level of CD62P was higher in the Abnormal Savda group (P<0.05). CD62P had different levels of changes among the four fluid groups and the control group, eg:Abnormal Savda> Abnormal Kan>Abnormal Balham>Abnormal Sapra>the control group. Compared to the control group, the level of plasma t-PA was significantly low in the Abnormal Savda and the non Abnormal Savda group (P<0.05). The level of plasma PAI-1 was increased significantly in these two groups (P<0.05). The level of t-PA varied among the four fluid groups and the control group, eg:Abnormal Savda< Abnormal Balham
4. Comparative Studies of phlegm-stasis syndrome and Abnormal Savda 4.1 Compared to the control group, CD62p, FIB and PAI were significantly increased in patients with Tanyuhuzu Syndrome and the Abnormal Savda Syndrome (P<0.01), but there was no statistical difference between them (P>0.05). These two groups had a lower t-PA level (P<0.05), again with no difference between them (P>0.05). ET-1 was significantly increased in these two groups (P>0.05), again there was no difference between them (P<0.05). The level of CD41 in these three groups didn't show a significant difference.
4.2 Compared to the control group, ET-l,CD62p, FIB and PAI were significantly increased in patients with Abnormal Savda Syndrome and non-Abnormal Savda Syndrome (P<0.05). The increase in the Abnormal Savda Syndrome group was more significant than the non-Abnormal Savda. Both groups had lower t-PA levels (P<0.05), the decrease in the Abnormal Savda Syndrome group was more significant, but when these two groups were compared there was no statistical difference (P>0.05). The level of CD41 in these three groups didn't change.
Conclusion
1. PTS is a common change in complex diseases such as tumors, diabetes, hypertension and coronary heart disease, PTS might be also one of the common pathophysiological basises of complex diseases. As far as the common changes of neuroen-docrine-immune pathway in complex diseases are concerned, it can be concluded that tumors, diabetes, hypertension and coronary heart diseases are systematic diseases. That is to say complex disease is not the only change in a certain organ but the overall change of the body.
2. Phlegm-stasis syndrome might be an important syndrome type of tumors, diabetes, hypertension and coronary heart diseases in Chinese Traditional Medicine. PTS is more obvious in Phlegm-stasis syndrome than that of the non Phlegm-stasis syndrome in complex diseases; especially the changes of CD62p, t-PA, PAI-l,PT,Fib, APTT which are more significant in Phlegm-stasis syndrome. From that result, we might consider applying the PTS indexes to quantitative judgment of Phlegm-stasis syndrome in complex diseases.
3. Abnormal Savda Syndrome might be an important syndrome type in tumors, diabetes, hypertension and coronary heart diseases in Uyghur Medicine. PTS is more obvious in the Abnormal Savda syndrome than that of the non Abnormal Savda syndrome; especially the changes of CD62p,t-PA,PAI-1,PT,Fib, APTT which are more significant in Abnormal Savda Syndrome. From that result, we might consider applying the PTS indexes to a quantitative judgment of Abnormal Savda syndrome in complex diseases.
4. Phlegm-stasis syndrome in Chinese Traditional Medicine and the Abnormal Savda syndrome in Uyghur Medicine are interactive according to their importance as a syndrome; they both happen in older patients and the changes of of PTS indexes are obvious in both. From this interaction we have concluded that the Phlegm-stasis syndrome in Chinese Traditional Medicine and the Abnormal Savda syndrome in Uyghur Medicine might be a pathological state of the same disease in different medical explanations. Is PTS one of the probable material foundations of these two? Are the Phlegm-stasis in Traditional Chinese Medicine and the Abnormal Savda in Uyghur Medicine the direct causes of PTS in complex diseases? It is necessary to study these assumptions further.
5. Vascular endothelial cell injury, platelet activation, increased blood viscosity and reduced fibrinolytic function are the reasons for the formation of blood clot. This process might be a common way for the Phlegm-stasis syndrome which includes Qi, gasification disorders and impaired fluid metabolism. This process also might be the one for the accumulation and burning of Abnormal Savda which eventually leads to the Abormal Savda syndrome. From that result we can assume that, prethromnotic state might be one of the material foundations of Phlegm-stasis and Abnormal Savda. Blood clot, Phlegm-stasis and Abnormal Savda are very similar, they are not only the Pathological products but also the risk factors.
6. Prethromboitic state exists both in the Non Phlegm- statis syndrom and the non Abnornal Savda syndrom in complex diseases, but the level of the prethromboitic state is lower in the Non Phlegm- statis syndrom and the non Abnornal Savda syndrom than that of the Phlegm- statis syndrome and the Abnornal Savda syndrome. Although there is no obvious clinical symptoms of the Phlegm- statis syndrome and the Abnornal Savda syndrome in Non Phlegm- statis syndrom and non Abnornal Savda syndrom in complex diseases, disorders in prethromboitic state indicate that tumors, diabetes, hypertension and coronary heart diseases patients might be in the prestage of the Phlegm- statis syndrome and the Abnornal Savda syndrome. As the diseases progress, there will be clinical manifestations of Phlegm- statis syndrome and Abnornal Savda syndrome in the Non Phlegm- statis syndrom and the non Abnornal Savda syndrome in complex diseases.
7. Traditional Chinese Medicine considers that "the Tongxinluo a long illness", "a long illness goes into the blood", "Abnormal Duo Tan", "Sputum causes all disease"; Uyghur Medicine considers that "black disease after a long time", "black in diseases". Phlegm-stasis syndrome in Chinese Traditional Medicine and Abnormal Savda syndrome in Uyghur Medicine happens a lot among tumors, diabetes, hypertension and coronary heart diseases. From that can we consider using Huo Xue Hua Tan and Hua Tan Bu Xu method in Traditional Chinese Medicine and Munziq and Mushil in Uyghur medicine whenever we encounter any complex diseases? Also pay close attention to the changes of TS indexes in order to increase the treatment effect of complex disease such as tumors, diabetes, hypertension and coronary heart diseases. This research has to be further researched.
引文
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