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气 (Qi): Vital energy in the body

Biomechanopharmacological annotation for the therapeutic principle of activating blood circulation to remove stasis Fulong Liao China Academy of Chinese Medical Sciences, Beijing, 100700, China Corresponding : liaofulong100@yahoo.com.cn. 气 (Qi): Vital energy in the body.

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气 (Qi): Vital energy in the body

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  1. Biomechanopharmacological annotation for the therapeutic principle of activating blood circulation to remove stasis Fulong Liao China Academy of Chinese Medical Sciences, Beijing, 100700, China Corresponding :liaofulong100@yahoo.com.cn

  2. 气(Qi): Vital energy in the body “The blood that is stored by the heart fills the pulse with the forces of life.” (Nei Jing) 帅 General 母 Mother " The blood circulates ceaselessly by the pushing of Qi." (THE MANIFESTATIONS AND PATHOGENESIS) 血 (Xue): Circulating blood

  3. Blood flow, shear and vascular events血流与血流剪应力 壁面剪应力 Shear stress τ = 4Qη / πr3

  4. Wall shear stress in different vessels 血管壁面剪切率与剪应力 血管部位 shear rate（s-1）stress（dyn/cm2） 大动脉artery 300-800 11.4-30.4 细动脉arteriole 500-1600 19.0-60.8 毛细血管capillary 0-1000 0-38.0 静脉vein 20-200 0.76-7.6 动脉狭窄stenosis 800-10000 30.4-380

  5. What is the impact of shear stress (SS) on endothelial cells? 剪应力对血管内皮细胞的影响 ● Platelet aggregation vWF/PGI2 ●Vessel tension ET / NO ●Fibrinolysis PAI/t-PA ●Cell adhesion ICAM-1，VCAM-1 ●Angiogenesis VEGF ●Atherosclerosis in low shear region

  6. General Effects of Shear Stress Arterial shear stress within a physiological range probably induces endothelial quiescence and an atheroprotective gene expression profile. Low SS might stimulate an atherogenic phenotype, whereas high SS might induce a prothrombotic state. Kazmierski,R (2003) Biomechanic shear stress in carotid arteries and atherosclerosis development. Postepy Hig Med Dosw. 57,713-725

  7. Affects of Disturbed Shear Stress Abnormal flow pattern can promote changes in endothelial gene expression, cytoskeletal arrangement, wound repair, leukocyte adhesion, and it affects the vasoreactive, oxidative and inflammatory states of the artery wall. Disturbed SS also influences the site selectivity of atherosclerotic plaque formation as well as its associated vessel wall remodeling, which can affect plaque vulnerability, stent restenosis and smooth muscle cell intimal hyperplasia in venous bypass grafts. Cunningham K.S. and Gotlieb A.I. (2005) The role of shear stress in the pathogenesis of atherosclerosis. Lab. Invest. 85, 9–23

  8. The importance of blood shear stress 血流剪应力的重要性 1。Normal range of shear stress is the requirement of healthy blood circulation. 维持健康血流可提供正常剪应力，使内皮细胞行使正常功能。 2。When abnormal interactions among blood/blood flow/blood vessel occur, we may consider shear stress as a multi-targeted drug. 在血液/血流/血管相互作用出现异常时，对于血流剪应力的调控，具有多靶向药物般的作用。

  9. Herbs of ABCRBS in Chinese medical literatures Canon ABCRBS: 11.2 % and 11.4 % accordingly

  10. Benefits gained from herbs of ABCRBS 活血化瘀药的药效 ●improvements in hemorheological parameters ●improvement in hemodynamics ● intervention on cerebral problems：cellular protection, atherosclerosis prevention，PTCA re-stenosis protection ● anti-thrombosis, thrombolysis ● regulation on immune funstions

  11. Example 1Inhibition of shear induced platelet aggregation and shear-dependent vWF secretion by TMP and DT

  12. fibrinogen aggregate Normal shear High shear Platelet aggregation under normal shear and under high shear

  13. Hand-colored drawing illustrating Rhizoma Ligustici Chuanxiong in a 1655 volume.

  14. Diallyl trisulfide (Garlicin) 大蒜素 S S S

  15. IC50 of TMP and DT for inhibition of SIPA in rabbit IC50=0.031e0.071 TMP DT IC50=0.123e0.025 τ

  16. Influence of TMP and DT on secretion of vWF by endothelial cell under different shear duration * * * * *, compared with control, P< 0.05

  17. Example 2Action of Buyanghuanwu Decoction on experimental cerebral infarction

  18. Buyanghuanwu Decoction补阳还五汤组方 Radix Astragali seu Hedysari 黄芪 60 g. Radix Angelicae Sinensis 当归6 g. Radix Paeoniae Rubra 赤芍 6 g. Lumbricus 地龙 3 g. Rhizoma Ligustici Chuanxiong 川芎3 g. Semen Persicae 桃仁3 g. Flos Carthami 红花 3 g.

  19. Phasic changes in infarcted area (red) and ischemic area (blue)

  20. 梗塞区的病理组织切片Pathological slide of the infarcted area 微动脉 血栓形成 微静脉

  21. Effect of Buyang Huanwu Tang on Plasma t-PA

  22. Chem. (e.g., drug) Joint action of mechanical and chemical factors on endothelial cell 力学与化学因素对血管内皮细胞的联合影响 Mech. (e.g., Flow) Nucleus Receptor Genes Functions Proteins Cell Focal Adhesions Integrins Extracellular matrix Modified slide from UCSD Bioengineering S. Chien

  23. Biomechanopharmacology 生物力药理学 ●Pharmacological intervention on biomechanical factors药理学措施对生物力学因素的干预 ●Biomechanical influences on pharmacokinetics and pharmacodynamics生物力学因素对药效与药代的影响 ● Research on relations among blood shear stress, secretion of endothelial cell, drug dosage and pharmacodynamics is the growing point of the new discipline. 有关血流剪应力、血管内皮细胞分泌功能、药物剂量与药效相互关系的研究是当前热点。

  24. Diseases are prevented when blood circulation is promoted. Huatuo 血脉流通, 病不得生 (华佗) Drawing of physical and breathing exercise on silk unearthed from a Han Tombs at Mawangduei, central China. It is an early archaeological evidence of exercise employed in healthcare in China some two thousand years ago. In the same period, Huatuo, the great surgeon, not only created five mimic-animal boxing as a physical fitness exercise, but also realized “Diseases are prevented as blood flow is promoted”. It is a wise foresight for biological effects of SS. (Courtesy of He ZJ et al. Sichuan People’s Publisher, 2001, 147)

  25. Concluding Remarks The effects of the therapeutic principle of ABCRScan be annotated from the angle of biomechanopharmacology. To benefit from the new discipline, we shall have to decide on the following issue: Should we go with the biomechanopharmacologically tailored exercise for controlling SS and rationally use herbs of ABCRS for protection of endothelial functions?

  26. Thank you for your kind attention!

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