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Journal of Chinese Integrative Medicine: Volume 6   November, 2008   Number 11

DOI: 10.3736/jcim20081102
Combination and transformation of toxin and blood stasis in etiopatho-genesis of thrombotic cerebrocardiovascular diseases
1. Da-zhuo SHI (Cardiovascular Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China E-mail: shidz666@sohu.com)
2. Hao XU (National Integrated Center of Cardiovascular Disease, China-Japan Friendship Hospital, Beijing 100029, China )
3. Hui-jun YIN (Cardiovascular Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China )
4. Jing-chun ZHANG (Cardiovascular Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China )
5. Ke-ji CHEN (Cardiovascular Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China )
Abstract: According to the basic theory of traditional Chinese medicine (TCM), the pathogenetic factors such as platelet activation, adhesion, congregation and thrombosis fall into the category of blood stasis, while the pathological changes such as tissue necrosis, oxidative stress injury and inflammation, etc, are far beyond the etiological category of blood stasis. The toxin or the combination and transformation of toxin and blood stasis of TCM are involved in the pathogenesis of thrombotic cerebrocardiovascualr diseases. It is significant to recognize and stress the combination and transformation of toxin and stasis in pathogenicity so as to enrich TCM etiology and improve TCM clinical efficacy in the treatment of cerebrocardiovascular and thrombotic diseases.
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Shi DZ, Xu H, Yin HJ, Zhang JC, Chen KJ. J Chin Integr Med/Zhong Xi Yi Jie He Xue Bao. 2008; 6(11): 1105-1108. Received May 12, 2008; published online November 15, 2008. Free full text (PDF) is available at www.jcimjournal.com. Indexed/abstracted in and full text link-out at PubMed. Forward linking and reference linking via CrossRef. DOI: 10.3736/jcim20081102

 

Correspondence: Da-zhuo SHI, MD, Professor; Tel: 010-62875599; E-mail: shidz666@sohu.com

 

基金项目: 国家科技部"973计划"资助项目 (No. 2006CB5044803)

Jump to Section
-   Top
-   Article & Author Info
-   Introduction
-   中医病因学发展促进了心脑血管病疗效的提高
-   心脑血管血栓性疾病病因不仅为“血脉瘀阻”,还有“毒损血脉”
-   瘀毒病因在心脑血管血栓性疾病过程中的互结从化
-   References
   

       传统中医病因学,不仅用直接观察病因的方法来认识病因,更重要的是根据中医传统理论从疾病临床表征推绎病因,从而为临床辨证施治提供依据。如《灵枢·本藏》云:视其外应,以知其内脏,则知所病矣。病因作用于人体,致机体产生病理变化,临床必出现相应的症状和体征(证候)。临床证候是果,由机体病变产生;病因是病机变化的原因。病因、病机和证候三者之间有必然联系。病因不同,所致疾病的证候表现亦不同,通过分析症状、体征,即可辨识疾病的原因。在传统中医临床发展过程中,病因认识学的每次发展,都会带来治疗方法学的改变和相应疾病治疗效果的提高,如温病学、疫病论及现代血瘀理论的认识等。随着现代医学的迅速发展,基因、蛋白、生物信号转导通路等在疾病过程中的作用逐渐被认识和发现,现代中医病因学的研究也逐渐向微观深入——尝试在传统中医理论指导下认识疾病的病理生理变化,形成和发展了一些疾病病因的认识,由此导致了现代一些疾病传统治疗模式的改变,提高了临床疗效和研究水平。这在心脑血管血栓性疾病病因学的认识方面表现得尤为突出。

 
   

1   中医病因学发展促进了心脑血管病疗效的提高
      对于冠心病(胸痹、心痛)和中风等心脑血管血栓性疾病病因的认识,从古到今经历了一个逐渐发展和深入的过程。如对冠心病(胸痹、心痛)病因病机的认识,20世纪6070年代以前,多遵循《金匮要略》上焦阳虚,阴寒闭阻,采用宣痹通阳或芳香温通方药治疗。此后,以陈可冀院士为代表的中医或中西医结合专家根据传统中医关于血瘀致病特点的认识和冠心病的病理生理改变,倡导活血化瘀为主治疗冠心病1,创制冠心号等系列活血化瘀方药用于临床。同时围绕冠心病血瘀致病的微观病理生理改变和临床特点,制定冠心病血瘀证病证结合诊治规范,提高了冠心病的中医治疗效果,促进了心脑血管血栓性疾病治疗方法学的创新。有关中风病病因的认识,唐宋以前,多以外风立论,强调正虚邪中,主张用风引汤大秦艽汤治疗;其后,逐渐认识到中风为内风所致,提倡采用平肝熄风或补肝肾熄风方药治疗;清·王清任则强调半身元气亏虚,血脉瘀滞不利,并创制补阳还五汤进行治疗;20世纪7080年代以后,以王永炎院士为代表的中医专家,根据中风病急性期患者神志不清、昏迷、大便干结等临床症状及组织坏死、水肿、过氧化脂质积聚等病理改变,提出毒损脑络的病理概念2,认为病因为互结,并创制清开灵、醒脑静等方药用于临床治疗,提高了临床疗效。可见,中医病因学的研究深入、发展和创新,是中医临床防治疾病疗效提高的基础。

Jump to Section
-   Top
-   Article & Author Info
-   Introduction
-   中医病因学发展促进了心脑血管病疗效的提高
-   心脑血管血栓性疾病病因不仅为“血脉瘀阻”,还有“毒损血脉”
-   瘀毒病因在心脑血管血栓性疾病过程中的互结从化
-   References
   

2   心脑血管血栓性疾病病因不仅为血脉瘀阻,还有毒损血脉
      我国缺血性心脑血管病的发病率约170/10万~390/10万,心脑血管病死亡率由八五期间第二位升至九五期间第一位3。心脑血管血栓性疾病多是在动脉粥样硬化(atherosclerosis, AS)基础上形成血栓,造成动脉管腔狭窄或阻塞,影响组织供血。AS基础上的血栓形成与炎症密切相关,两者相互促进,互为因果:一方面,炎症因子释放可以诱发血小板黏附聚集和血栓形成;另一方面,血栓形成也是炎症激活的主要因素。以往认为血小板主要参与凝血止血和血栓形成,新近则发现血小板本身也是一个炎症细胞,血小板的活化可介导炎症细胞趋化、黏附和浸润,致组织损伤45。心脑血管血栓性疾病发病过程中的血小板活化、黏附、聚集和血栓形成,传统中医药学多将其病因病机归于血脉瘀阻,在此认识指导下,形成了理气活血、益气活血和温阳活血等系列治法和有效方药;但组织坏死、过氧化应激损伤、炎症反应等病理改变,远非单一血瘀病因所能概括。结合传统中医有关邪病因的认识和心脑血管血栓性疾病发病的临床特点,应当存在邪致病或从化联合致病的病因病机。
      高度敏感性C反应蛋白(high sensitive C-reactive protein, hs-CRP)是目前检测炎症反应的一个代表性生物标记物,20031月美国心脏协会和疾病控制中心推荐hs-CRP为心血管疾病二级临床检测指标(证据B级)6。炎性反应在血栓性疾病尤其是在心脑血管血栓性疾病的发病过程中具有重要地位。心脑血管血栓性疾病血液致病因素包括低密度脂蛋白、血糖、同型半胱氨酸及病原微生物刺激等,上述病理因素作用于血管内膜使血管内皮发生结构和功能改变,继而脂质沉积、血小板活化聚集和血栓形成,诱导大量炎性因子产生,促进炎性细胞活化,造成血管内膜发生慢性修复性炎症反应78;而炎症又是诱发AS斑块不稳定和斑块破裂的一个主要原因。斑块破裂,激发血栓形成,堵塞动脉管腔,可导致急性冠状动脉综合征、脑梗死及周围动脉血栓栓塞等严重临床心脑血管病事件的发生8
      针对心脑血管血栓性疾病,现代医学采用抗血小板、静脉溶栓、动脉溶栓、经皮动脉介入和冠状动脉搭桥等方法治疗,虽多数能达到开通堵塞及狭窄血管和恢复缺血区域血流的目的,但目前仍存在许多无法真正解决而又必须面对的问题:(1)上述方法仍是心脑血管事件发生后的补救措施,即使治疗及时,罪犯血管的堵塞已不同程度地损伤了机体组织9;(2)目前介入治疗方法针对的是较大的主干血管,无法真正解决组织无复流缓慢复流现象1011;(3)动脉血栓形成致组织变性坏死、炎症细胞浸润、氧自由基爆发和细胞凋亡等连锁病理反应,皆可严重影响相关脏器的功能和临床预后。可见,炎症反应、氧化应激和组织变性损伤是动脉血栓性疾病的必然结果,贯穿整个病理过程的始终。
      心脑血管血栓性疾病发病的临床特点和血栓闭塞引发的组织损伤坏死、炎症瀑布反应、氧化脂质沉积和细胞凋亡等病理损害,与中医邪致病起病急骤、传变迅速、直中脏腑和腐肌伤肉等特点多有相似之处。因此,将两种病因结合,可更全面地诠释心脑血管血栓性疾病的中医病因病机,更有利于指导心脑血管栓塞性疾病的中医治疗。一些小样本临床观察表明,清热解毒方药在防治不稳定性心绞痛和脑卒中方面具有一定临床疗效1213。我们采用不同活血化瘀中药配伍干预ApoE基因缺陷小鼠AS不稳定斑块形成,证明活血解毒中药消减和稳定AS斑块的作用优于单纯的活血化瘀中药1415,以效析因,从实验角度也证实了瘀毒病因兼夹在动脉血栓性疾病发病中的作用。

Jump to Section
-   Top
-   Article & Author Info
-   Introduction
-   中医病因学发展促进了心脑血管病疗效的提高
-   心脑血管血栓性疾病病因不仅为“血脉瘀阻”,还有“毒损血脉”
-   瘀毒病因在心脑血管血栓性疾病过程中的互结从化
-   References
   

3   瘀毒病因在心脑血管血栓性疾病过程中的互结从化
         作为病因,皆具有兼夹性和依附性,它们既可是疾病的病理产物,也可是致病的病因。毒邪致瘀原因可归纳为以下几个方面:(1)毒邪煎熬血液,血凝成瘀;(2)毒邪伤络,血溢成瘀;(3)毒邪伤津耗阴,阴伤血滞为瘀;(4)毒壅气机,血脉凝滞;(5)热毒损脏,血行失司。另一方面,瘀血阻滞脉络,血行缓滞或不循常道,溢出脉外,瘀久不消,组织器官变性坏死,则蕴化成毒。由此可知,在疾病发生发展过程中可相互从化,互为因果,形成恶性循环。其中,为有形之灶,为病情转变和恶化的关键。如冠心病稳定性心绞痛,基本病理改变是AS造成冠状动脉固定性狭窄,其心绞痛发生的诱因、疼痛性质、部位和缓解方式在相当一段时间维持不变;冠状动脉内一旦由稳定性AS斑块(固定性狭窄)转变为不稳定斑块,继发血栓形成,则病情发生急剧变化,心绞痛程度加重,持续时间延长,甚至出现心肌梗死、猝死等严重心脏事件,病情转为凶险多变。综合互结致病在心血管血栓性疾病的临床表现,主要有疼痛剧烈、固定性刺痛、出血、厥脱、昏迷,舌紫绛而暗有瘀斑或紫黑、舌苔厚腻或垢腻,脉涩、结代或无脉等;其次可见面色黧黑、肌肤甲错、唇萎甲紫、狂躁善忘、口气臭秽、青筋暴张等。从相关文献资料中归纳致病的临床表征,审症析因,也可发现心脑血管血栓性疾病大多有致病的临床症状,且二者常交互存在,中有中有。见表1
    

1   心脑血管血栓性疾病病因的临床表征和微观病理改变 

 

致病特点

广泛性、兼夹性、久病入络、久病成瘀

依附性、酷烈性、从化性、秽浊性、兼夹性、顽固性

临床症状

痛有定处、固定性刺痛或绞痛、皮下瘀斑、精神狂躁或健忘、唇及肢端紫绀、唇和齿龈及眼周紫黑、舌下及其他部位静脉曲张等

发病急骤,见症多端,变化迅速,神志昏迷或谵妄、烦躁不安和疼痛剧烈等

舌象

舌质紫暗或舌体瘀斑、瘀点

舌质紫绛或舌苔垢腻、焦燥、起芒刺

脉象

脉涩或结代、无脉

脉浮大或弦滑而数或六脉沉细

微观病理

微循环障碍、血液流变学异常、血小板聚集性增高、血管栓塞、血液凝固性增高或纤溶活性降低等

炎性介质、血管活性物质过度释放、超氧化物释放、自由基和代谢物质堆积、钙离子超载或兴奋性氨基酸神经毒堆积等

 

    注重病因在心脑血管血栓性疾病致病过程中的互结、从化,在传统中医病因学理论指导下认识心脑血管血栓性疾病的病理生理改变,采用现代流行病学和信息生物学方法,总结归纳中医宏观临床表征变化和微观病理生理变化的相关性和演变规律,从互结从化角度研究总结心脑血管血栓性疾病新的治法和方药,进而按照现代循证医学要求客观评价不同活血解毒配伍中药的临床疗效,反证在心脑血管血栓性疾病发病中的作用,对丰富中医心脑血管血栓性疾病病因病机理论,进而提高临床疗效,是一非常值得探索的工作。

Jump to Section
-   Top
-   Article & Author Info
-   Introduction
-   中医病因学发展促进了心脑血管病疗效的提高
-   心脑血管血栓性疾病病因不仅为“血脉瘀阻”,还有“毒损血脉”
-   瘀毒病因在心脑血管血栓性疾病过程中的互结从化
-   References
   
References
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10. Porter TR, Li S, Oster R, et al. The clinical implications of no reflow demonstrated with intravenous perfluorocarbon containing microbubbles following restoration of Thrombolysis In Myocardial Infarction (TIMI) 3 flow in patients with acute myocardial infarction[J]. Am J Cardiol, 1998, 82(10) : 1173-1177.
    
11. Kenner MD, Zajac EJ, Kondos GT, et al. Ability of the no-reflow phenomenon during an acute myocardial infarction to predict left ventricular dysfunction at one-month follow-up[J]. Am J Cardiol, 1995, 76(12) : 861-868.
    
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13. Lu XH. Clinical effect and mechanism on treating unstable angina pectoris by Huanlian Jiedu Capsule[J]. Shandong Zhong Yi Yao Da Xue Xue Bao, 2005, 29(6) : 457-460. Chinese with abstract in English.
  
14. Wen C, Xu H, Huang QF, et al. Effects of herbs of activation blood on atherosclerotic plaque morphology in ApoE gene-deficient mice[J]. Zhongguo Bing Li Sheng Li Za Zhi, 2005, 21(8) : 1640. Chinese.
  
15. Wen C, Xu H, Huang QF, et al. Effect of drugs for promoting blood circulation on blood lipids and inflammatory reaction of atherosclerotic plaques in ApoE gene deficiency mice[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2005, 25(4) : 345-349. Chinese with abstract in English.
  
Jump to Section
-   Top
-   Article & Author Info
-   Introduction
-   中医病因学发展促进了心脑血管病疗效的提高
-   心脑血管血栓性疾病病因不仅为“血脉瘀阻”,还有“毒损血脉”
-   瘀毒病因在心脑血管血栓性疾病过程中的互结从化
-   References
   
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