冠心病不稳定性心绞痛气虚血瘀证及炎症相关性研究

【作者】 其其格；

【导师】 毕力夫； 王伟； 胡立胜；

【作者基本信息】 北京中医药大学 ， 中西医结合基础， 2010， 博士

【摘要】 冠心病是多种危险因素所导致的慢性疾病。尽管很多因素(如年龄、吸烟、饮酒、肥胖、高血压、糖尿病、高血脂及遗传等)已被证明与冠心病的发生、发展有关,但还不能对所有冠心病的发生作出满意的解释。因此,对导致冠心病发生、发展的其他生物学标志物,尤其是炎症标志物(如白细胞计数、C反应蛋白、白细胞介素)等的研究已成为当前研究的热点。冠心病属中医“胸痹”、“心痛”范畴,中医学运用病证结合防治冠心病心绞痛具有独特优势,而中医辨证论治又是中医理论的核心和精髓。不同中医证候可能存在不同的生物学基础。本论文对125例冠心病不稳定性心绞痛患者进行中医证候调查,对其理化指标进行统计分析,并做白介素-1、6、肿瘤坏子因子-a、细胞间黏附因子-1、血清淀粉样蛋白A等炎症相关指标,旨在探讨冠心病不稳定性心绞痛患者证候分布特点及不同证候间是否存在不同理化指标及炎症相关因子的差异,并对冠心病不稳定性心绞痛不同中医证候与理化指标、炎症相关因子做相关性分析。为临床寻找简便、有效的判断冠心病不稳定性心绞痛不同证候及预后的指标。结果：①125例冠心病不稳定性心绞痛患者中医证候特点：涵盖血瘀证、痰浊证、气滞证、寒凝证、气虚证、阴虚证、阳虚证等7个证候；其中单证31例,占24.60%,以血瘀证为主,占51.61%,其次气虚证,占12.90%；两证组合64例,占51.20%,以气虚血瘀证最多,占48.88%,其次痰瘀互阻证,占14.06%；三证组合22例,占16.80%,以气虚血瘀痰浊证最多,占28.57%,其次为气虚血瘀气滞证,占23.81%；四证组合和五证组合少见,各占4.76%和2.38%；从两证到五证组合在气虚血瘀证的基础上以气虚-阴虚-气滞为组合变化轴线；气虚血瘀并见者51例,占总病例数的40.80%；虚实兼夹证71例,占总病例数的56.80%；②证候与理化指标间Sperman相关分析显示：血瘀证与血清总胆固醇水平(TC)、载脂蛋白B(apoB100)、直接胆红素(DBIL)相关；气虚证与平均红细胞血红蛋白浓度(MCHC)、直接胆红素(DBIL)等相关；气虚血瘀证与外周血红细胞计数(RBC)、红细胞平均体积(MCV)、平均红细胞血红蛋白浓度(MCHC).直接胆红素(DBIL)等相关；Logistic回归结果显示：单核细胞(M)、胆红素、载脂蛋白B (apoB100).载脂蛋白AI(apoAI)、白细胞计数(WBC)等为血瘀证主要影响因素；气虚证主要影响因素依次为外周血红细胞计数(RBC)、平均红细胞血红蛋白含量(MCH)、红细胞平均体积(MCV)等；气虚血瘀证影响因素依次为胆红素、红细胞计数(RBC)、平均红细胞血红蛋白含量(MCH)、红细胞压积(HCT)、单核细胞(M)、红细胞平均体积(MCV)等；③证候与炎症相关性研究中结果显示：血瘀证与白细胞介素-6(IL-6)、肿瘤坏死因子-a(TNF-a).细胞间黏附因子-1(ICAM-1)及纤维蛋白原(FIB)相关；气虚证与白细胞介素-6(IL-6)、肿瘤坏死因子-a(TNF-a).细胞间黏附因子-1(ICAM-1)、超敏C反应蛋白(hs-CRP)及核因子-KB(NF-KB)相关；气虚血瘀证与白细胞介素-6(IL-6)、肿瘤坏死因子-a(TNF-a).细胞间黏附因子-1(ICAM-1)相关；④炎症指标间及血脂相关性分析结果显示：血清淀粉样蛋白A(SAA)与血清甘油三酯(TG)正相关(r=0.246,p=0.004)、与白细胞介素-1(IL-1)正相关(r==0.192,p=0.025),与载脂蛋白AI(apoAI)负相关(r=-0.182,p=0.034);超敏C反应蛋白(hs-CRP)与载脂蛋白AI(apoAI)负相关(r=-0.179,p=0.037),与载脂蛋白B100 (apoB100)负相关(r=-0.192,p=0.025),与细胞间黏附因子-1(ICAM-1)正相关(r=0.323,p=0.000);纤维蛋白原(FIB)与载脂蛋白AI(apoAI)负相关(r=-0.188,p=0.029),与白细胞介素-1(IL-1)、细胞间粘附因子-1(ICAM-1)正相关(r=0.301,p=0.000;r=0.339,p=0.000);白细胞介素-1(IL-1)与载脂蛋白(apoAI)负相关(r=-0.180,p=0.036);白细胞介素-6(IL-6)与载脂蛋白(apoAI)负相关(r=-0.178,p=0.039);细胞间黏附因子因子(ICAM-1)与高密度脂蛋白(HDL)负相关(r=-0.217,p=0.011)。结论：①125例冠心病不稳定性心绞痛患者证候涵盖血瘀证、痰浊证、气滞证、寒凝证、气虚证、阴虚证、阳虚证等7个证候；证候组合以两证组合为主；从两证到五证组合在气虚血瘀证的基础上以气虚-阴虚-气滞为组合变化轴线；气虚血瘀为冠心病不稳定性心绞痛主要病机；②冠心病不稳定性心绞痛血瘀证与外周血白细胞、清总胆固醇水平、载脂蛋白B、胆红素水平相关；气虚证与外周血红细胞计数、平均血红蛋白浓度、血小板计数、胆红素水平相关；气虚血瘀证与外周血红细胞计数、平均血红蛋白浓度、白细胞计数、胆红素水平相关,提示冠心病不稳定性心绞痛患者不同证候有自己的生物学基础；③冠心病不稳定性心绞痛发生、发展与炎症相关,且冠心病不稳定性心绞痛患者不同中医证候存在炎症相关因子表达差异：血瘀证与肿瘤坏死因子-a、纤维蛋白原相关；气虚证与纤维蛋白原、超敏C反应蛋白、白细胞介素-6、肿瘤坏死因子-a、细胞间黏附因子-1、核因子-KB相关；气虚血瘀证与白细胞介素-1、6、肿瘤坏死因子-a、细胞间黏附因子-1相关；④各种炎症相关指标之间及炎症指标与血脂之间存在相关关系。冠心病不稳定性心绞痛的发生、发展与炎症反应有关。冠心病不稳定性心绞痛血瘀证、气虚证、气虚血瘀证候与炎症反应有关。结果进一步支持了以动脉粥样硬化为基础的冠心病是一种慢性炎症过程这一理论假说。并提示冠心病不稳定性心绞痛不同证候中释放急性时相蛋白、炎症因子有一定的差异。更多还原

【Abstract】 Coronary heart disease(CHD) is a chronic diseases caused by many risk factors. Although many factors (such as age, smoking, drinking, obesity, hypertension, hyperlipidemia, diabetes and genetic, etc.) has been proven with the occurrence of CHD, but also the occurrence of CHD can not be made for all satisfactory explanation. Therefore, leading to CHD and other biological markers, particularly, inflammatory markers (such as white blood cell count, C-reactive protein, interleukin) and other research has become a research hotspot. CHD are the category of "Chest", "heartache" in Traditional Chinese Medicine(TCM). The treatment according to syndrome differentiation is the core and essence of TCM theory. Different syndromes may exist in different biological basis. TCM have the unique advantages to put to use syndrome and disease to prevent and cure Unstable angina (UA).The study invests the syndromes of 125 patients in UA of CHD, makes statistical analysis of their biological parameter detections,and detects their IL-1, IL-6, TNF-a, cell adhesion molecule-1, serum amyloid A, etc. inflammation-related indexes.Aim to investigate the class distribution of different syndromes,and the relation between syndromes with biological parameter detections and inflammation-related indexes. To find simple and effective indexes to judge UA different syndromes to use for clinical.Result:①125 patients with UA patients with blood stasis syndrome, phlegm syndrome, and Qi stagnation syndrome, cold coagulation card syndrome, qi deficiency syndrome, yin deficiency syndrome, yang deficiency syndrome; documents 31 cases, accounting for 24.6%, mainly by blood stasis syndrome, accounting for 51.61%, followed by qi deficiency syndrome, accounting for 12.9%; two card combinations of 64 cases, accounting for 51.2%, up to Qi deficiency and blood stasis syndrome, accounting for 48.88%, followed by phlegm and blood stasis syndrome, accounting for 14.06%; three card combination 22 cases of qi deficiency、blood stasis and phlegm syndrome, accounting for 28.57%, followed by blood stasis and Qi stagnation syndrome, accounting for 23.81%; four card combinations and rare combination of five cards, accounting for 4.76% and 2.38%; On the basis of Qi deficiency and blood stasis syndrome,two to five card combination changes at Qi deficiency-yin Deficiency-Qi stagnation axis; 51 patients are Qi deficiency and blood stasis syndrome,which account for the total number of cases of 40.80%; 71 patients are actual situation and evidence folders, which account forthe total number of cases of 56.80%.②Syndrome associated with the biological parameter detections Sperman analysis and Lgistic stepwise regression analysis showed:blood stasis syndrome relate with CHO, DBIL and MCV; Qi deficiency syndrome relate with RBC, MCH, PLT, DBIL; Qi deficiency and blood stasis syndrome relate with RBC, MCH, PLT, DBIL. Logistic regression analysis showed:Mononuclear cells (M), bilirubin, apolipoprotein B (apoB100), apolipoprotein AI (apoAI), white blood cell count (WBC),etc are the main infiuence factors of blood stasis syndrome of CHD; the main infiuence factors of qi deficiency syndrome were red blood cell count (RBC), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), the infiuence factors of Qi deficiency and blood stasis syndrome were bilirubin, red blood cell count (RBC), mean corpuscular hemoglobin (MCH), hematocrit (HCT), monocytes (M), mean corpuscular volume (MCV),etc.③The result of relation between Syndrome with inflammation-related indexes showe:blood stasis syndrome relate with IL-6, TNF-a, intercellular adhesion molecule-1,FIB; Qi deficiency syndrome relate with IL-6, TNF-a, intercellular adhesion molecule-1, hs-CRP,NF-KB; Qi deficiency and blood stasis syndrome relate with IL-6, TNF-a, intercellular adhesion molecule-1.④Inflammation and lipid indexes correlation analysis showed that:SAA positive correlation with TG (r= 0.246, p= 0.004) and IL-1 (r= 0.192, p= 0.025), but negative correlation with apoAI (r=-0.182, p= 0.034); hs-CRP negative correlation with apoAI and B100 (r=-0.179, p= 0.037; r=-0.192, p= 0.025), but positively correlated with ICAM-1 (r = 0.323, p= 0.000); FIB negative correlation with apoAI (r=-0.188, p= 0.029), but positively correlation with IL-1, ICAM-1 (r= 0.301, p= 0.000; r= 0.339, p= 0.000). IL-1 negative correlation with apoAI (r=-0.180, p= 0.036); IL-6 negative correlation with apoAI (r=-0.178, p= 0.039); ICAM-1 negative correlation with HDL (r=-0.217, p= 0.011). Conclusion:①125 patients with UA patients with blood stasis syndrome, phlegm syndrome, and Qi stagnation syndrome, cold coagulation card syndrome, qi deficiency syndrome, yin deficiency syndrome, yang deficiency syndrome; On the basis of Qi deficiency and blood stasis syndrome,two to five card combination changes at Qi deficiency-yin Deficiency-Qi stagnation axis;Qi deficiency and blood stasis syndrome is the main pathogenesis.②The blood stasis syndrome of UA relate with CHO, DBIL and MCV; Qi deficiency syndrome relate with RBC, MCH, PLT, DBIL; Qi deficiency and blood stasis syndrome relate with RBC, MCH, PLT, DBIL.CHD blood stasis syndrome、qi deficiency syndrome、Qi deficiency and blood stasis syndrome have its own biology mechanism.③UA occurrence and development may be associated with inflammation, and the existence of different syndromes abnormal expression of inflammation-related factors. blood stasis syndrome relate with IL-1; Qi deficiency syndrome relate with IL-6, TNF-a, intercellular adhesion molecule-1, NF-KB.④There is correlation between various inflammation-related indicators,also between inflammation-related indicators and blood lipids.CHD occurrence, development may be inflammation-related. Syndrome of blood stasis, qi deficiency, qi deficiency and blood stasis are inflammation-related. The results further support the Atherosclerosis is a chronic inflammatory process. Different syndromes of UA have the inflammatory process and release acute phase proteins.更多还原