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Interventional or thrombolytic therapy for acute myocardial infarction （AMI） has the effect of opening occluded coronary arteries. However， due to no myocardial regurgitation， ischemia/reperfusion injury and microvascular structure and function destruction， leading to myocardial fibrosis following AMI， ventricular remodeling， and even cardiac failure may occur. Collaterals doctrine is used to guide the investigation into traditional Chinese medicine pathogenesis and clinical treatment of myocardial fibrosis following AMI. Consequently， it proposes the pathogenesis characteristic of "Qi deficiency and blood stasis， collaterals obstruction" and medication principle of "dispersing and dredging"， to develop the formula of Tongxinluo. Fundamental and clinical researches have demonstrated it can effectively protect the structure and function of myocardial microvascular endothelial cells， improve no reflow and reperfusion injury， and inhibit myocardial fibrosis after AMI， which further supports scientific value of the collaterals doctrine.
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Objective:Guided by nutrient-defense stages in the vessel-collateral theory， the modern medical cases of unstable angina pectoris（UAP） were systematically collated and analyzed to explore the rules of syndrome and treatment of UAP and the molecular mechanism of core Chinese herbal combination in the treatment of UAP based on network pharmacology. Method:All medical cases with UAP treated by Chinese medicinal compounds were retrieved from PubMed，China National Knowledge Infrastructure （CNKI），Wanfang Data， VIP， and SinoMed published between database inception and November 2020. The syndromes of medical cases were determined based on the nutrient-defense stages of the vessel-collateral theory. Rules of syndrome and treatment of UAP were investigated by data mining methods， such as frequency statistics， cluster analysis， and enhanced FP-Growth algorithm. The molecular mechanism of core Chinese herbal combination in the treatment of UAP was analyzed by network pharmacology. Result:The first four syndromes of UAP with high frequencies were deficiency and stagnation of collateral Qi， blood stasis obstructing collaterals， depression and stagnation of collateral Qi， and turbid phlegm obstructing collaterals. The Chinese herbal medicines with high frequencies included Salviae Miltiorrhizae Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Chuanxiong Rhizoma， and Astragali Radix， which were effective in resolving stasis， dredging collaterals， replenishing Qi， consolidating defensive Qi， regulating Qi， relieving depression， and dispelling phlegm. The association analysis indicated that the core Chinese herbal combination in the treatment of UAP was Salviae Miltiorrhizae Radix Chuanxiong Rhizoma-Astragali Radix. Four Chinese herbal combinations were obtained by cluster analysis. As revealed by network pharmacology， the key components of Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Astragali Radix in the treatment of UAP included quercetin， luteolin， and tanshinone Ⅱ<sub>A</sub>， and the key targets included serine/threonine-protein kinase 1 （Akt1）， mitogen-activated protein kinase 1 （MAPK1）， Jun， interleukin （IL）-6， and MAPK8. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis showed that phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathway might serve as the main pathway for its therapeutic efficacy. Conclusion:The basic pathogenesis of UAP is deficiency/depression and stagnation of collateral qi and turbid phlegm obstructing collaterals. The treatment should follow the principles of replenishing Qi， resolving stasis， and dredging collaterals， assisted with regulating Qi and resolving phlegm. The therapeutic efficacy of Salviae Miltiorrhizae Radix-Chuanxiong Rhizoma-Astragali Radix was achieved via multi-component， multi-target， and multi-pathway. This study is expected to inspire future UAP-related studies at the molecular level based on vessel-collateral theory.
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Based on the syndrome and treatment system of collateral disease， and inheriting the development of the bloodline theory of traditional Chinese medicine （TCM）， academician WU Yi-ling systematically constructed the vessel-collateral theory of TCM and proposed that its core theory was the theory of Yingwei， that is， "Ying in the vein， and Wei outside the vein" （Huangdi Neijing·Lingshu·Yingwei Shenghui）， "obstructing of Yingwei， congelation of blood" （Treatise on Febrile Diseases· Pulse Differentiation Method）， "pathogen transferring through blood vessels， obstructed by blocking" （Jinkui Yaolue·Zangfu Jingluo Xianhou Bingmaizheng First）， and "damage of the heart， adjust its Yingwei". Based on the consistency of vessel-collateral as the channel of blood circulation in TCM with the blood vessels in western medicine， and guided by the Yingwei theory of vessel-collateral theory， the diagnostic criteria of syndrome differentiation of disease of vessel-collateral and vascular system represented by coronary heart disease， arrhythmia， heart failure and others was established to guide the prevention and treatment of vascular diseases. Based on the above analysis， guided by the Yingwei theory of vessel-collateral theory， and on the basis of related researches of vessel-collateral and vascular system， this paper discussed the etiology and pathogenesis of chronic coronary syndrome （CCS） in TCM. Taking useful collateral with unblocking as the treatment principle， the representative Tongluo prescription （Tongxinluo） was constructed， the research progress of Tongxinluo from various aspects such as animal experiment research， pharmacological research and clinical evidence-based research was summarized， a comprehensive system from etiology， pathogenesis， syndrome differentiation to treatment was formed， in order to provide new ideas for the clinical treatment of CCS.
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Related records about discipline of diagnosis and treatment of exogenous febrile diseases by traditional Chinese medicine (TCM) were reviewed to summarize TCM knowledge about etiology, pathogenesis, progress and treatment of infectious epidemic diseases among exogenous febrile diseases. In consideration of onset time and major clinical manifestations of novel coronavirus pneumonia (NCP), this disease is considered as within the scope of pestilence in TCM, it is located in the lung, with etiology being poison of winter-warm syndrome, the viruses enter body via mouth and nose, and invade pulmonary collaterals. Based on the syndrome characteristics proposed in diagnosis and treatment schemes of various regions as well as the researches on medication rules, the present study points out the core pathogenesis of NCP is epidemic toxin invading the lung, pathogenic heat obstructing the lung and toxic heat blocking the lung. It also analyzes theoretical formula features of TCM Lianhua Qingwen and related clinical and experimental research results, in order to prove the clinical value of this drug in the outbreak of NCP.
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Health-preservation thoughts of the four major schools (Confucianism, Buddhism, Taoism and Medicine) have important reference values for the health preservation and health care industry. The core of health-preservation thought of the Taoism is taking mind training as the focus and physical exercise as the supplementary means, Taoism is nature-admiring, emphasizes the idea of natural laws and inaction and humanity follows natural laws, as well as advocates following nature's courses, realizing the passive inaction, and keeping calmness, also, it advocates the way of keeping good health through preserving vital essence, energy and mentality, in order to achieve the purpose of training vital essence into energy, training energy into mentality and maintaining complete vital essence, energy and vitality. Through long-term development, Medicine has formed a relatively complete set of theoretical and systematic health-preservation methods. The holistic concept of Medicine emphasizes the uniformity among human, nature and society, considers human body as an organic whole, and advocates the health-preservation thoughts of living in harmony with nature, accommodating the four seasons, keeping good circulation of energy and blood, dredging collaterals, nourishing essence and replenishing energy, accumulating healthy energy and repelling pathogenic factors, maintaining the inseparability of the body and spirits, as well as taking proper exercises and keeping mental calmness. Based on the health-preservation thoughts of the four major schools, this paper summarizes the modern health-preservation guiding thoughts of dredging collaterals, nourishing essence, taking exercises and keeping mental calmness, in order to provide the theoretical guidance for traditional Chinese medicine health-preservation services.
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Traditional health preservation thoughts of four major schools (Confucianism, Buddhism, Taoism and medicine) were systematically summarized. The proposed health-preserving ideas of physical health maintenance by Confucianism (self-cultivation, moderation and harmony), mental health maintenance by Buddhism (keeping still and in deep meditation, insight, kindness and help), health preservation by Taoism (following the nature, enhancing spirit and energy) and life protecting by medicine (dredging collaterals, Qi and blood, possessing both the form and the spirit), and the health-preserving methods under the guidance of such ideas have important guiding value for current industry of traditional health care.
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Meridians include (Qi) channels and blood (vessels). In Duyi Suibi, ZHOU Xue-hai of qing Dynasty named the terminal of Qi channel as"fine collateral of Qi" and the terminal of blood vessel as"fine collateral of blood". Qi channels of the heart cover extensive regulating mechanisms including cardiac pacing and conducting system. Blood vessels of the heart cover circulation system of coronary artery. Cardiac Qi channels and blood vessels are coordinated mutually, and Ying and Wei run together, to jointly maintain normal functions of the heart. Abnormal Yingwei caused by various pathogenic factors leads to occurrence of arrhythmia. Based on the Yingwei theory of vessel-collateral theory, this paper puts forward treatment based on syndrome differentiation of arrhythmia guided by therapeutic principle of"regulating Yingwei in case of heart damage" (Nanjing·14thNan) as well as addresses both symptoms and root causes by prescriptions for regulating Wei, Qi, Ying and blood through sufficiently considering modern pathogenic factors and pathogenic characteristics, in order to provide beneficial reference for clinical diagnosis and treatment.
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The blood-vein theory is inherited and developed. Combined with the related theory features of Qi and blood of traditional Chinese medicine(TCM), the progress results in two national 973 plan projects undertaken are learned from, the vessel-collateral theory guiding the prevention and treatment of vascular lesions is systematically built, the academic development of TCM collateral disease discipline is pushed from "treatment of symptoms of collateral disease" to study on "vessel-collateral theory", a new stage in the history. The pathogenesis, basic pathogenesis, clinical syndrome and syndrome differentiation therapy of vessel-collateral lesions are systematically studied, Yingwei theory, the core content of vessel-collateral theory, is proposed, the syndrome differential diagnosis standard of "vessel-collateral-vascular system disease" is established, and the blood-vessel theory of TCM is improved. The development of Yingwei theory of vessel-collateral theory is deepened. The theory of Yingwei sympathia and Yingwei's "opening by collaterals, intersecting and generating" are proposed to guide the study on prevention and control of vascular lesions. With tertiary collaterals-microvessel as a breakthrough point of research, four types of microscopic pathological features of microvessels are proposed. It is confirmed that dredging collaterals and protecting tertiary collaterals-microvessel is the common key mechanism for the treatment of major diseases of heart, brain and kidney(sugar). It protects microvessels, improves blood flow perfusion, protects tissue cells, and improves the viscera function. Dredging collaterals and protecting microvascular endothelial cells is the core mechanism of treating tertiary collaterals-microvessel lesions. It is proposed that protection of microvascular endothelial cells is a new strategy to solve the problem of microvascular lesions. After more than ten years, four studies of evidence-based medicine have been completed to solve the clinical problem of acute myocardial infarction without reflow. New drugs are provided to the international medical problem of cardiac insufficiency with premature ventricular contraction. The gap of fast and slow treatment, integration and rhythm adjustment of sinus bradycardia with premature ventricular contraction is filled. The clinical treatment effect of chronic heart failure is significantly improved, a major breakthrough in the treatment of microvascular lesions by TCM is achieved, and it is fully recognized and highly evaluated by the medical profession at home and abroad. It promotes the specialized subject platform construction and society development under the guidance of Yingwei theory of vessel-collateral theory, as well as the clinical application of syndrome differentiation diagnosis and treatment method and drugs of vessel-collateral lesions, and has significant social and economic benefits.
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"Vessels Collateral Theory", as the inherit and development of "blood vessels" in Huangdi Neijing, is a systematic system by integrating severe vascular diseases. In this article, by taking cardiovascular diseases (CVD) as a cut-in point, roles of "minute collateral-microvascular" lesions in the occurrence and development of CVD were further explored. The interventional effect of collateral-unblocking medicines under the guidance of Vessels Collateral Theory was also in-depth explored, hoping to leading Chinese medical prevention and treatment of CVD.
Asunto(s)
Humanos , Enfermedades Cardiovasculares , Quimioterapia , Medicina Tradicional China , InvestigaciónRESUMEN
<p><b>OBJECTIVE</b>To observe the effects of Tongxinluo (TXL) on angiogenesis and the volume of blood perfusion in ischemic stroke rats.</p><p><b>METHODS</b>The model of middle cerebral artery occlusion (MCAO) was established using craniotomy ligation of the middle cerebral artery on one side. After screening, the male SD rats were randomly divided into the sham-operation group, the model group, the large dose TXL group, the middle dose TXL group, the low dose TXL group, and the Nimodipine group. The expression of microvascular density (MVD, CD31) of the MCAO rats was detected using immunohistochemical assay after 14 days of medication. The microvascular morphology and the volume of blood perfusion in the brain tissue were observed under laser scanning confocal microscope (LSCM).</p><p><b>RESULTS</b>The positive CD31 expression was intense with significant coloring in the large dose TXL group, the middle dose TXL group, and the Nimodipine group, better than that of the model group. The blood perfusion volume in the ischemic brain cortex could be promoted in the large dose TXL group, the middle dose TXL group, and the Nimodipine group (P<0.01, P<0.05). The optimal effects were shown in the large dose TXL group (P<0.01).</p><p><b>CONCLUSION</b>TXL significantly increased the MVD of the ischemic brain tissue, promoted the post-ischemic angiogenesis, and increased the volume of blood perfusion of ischemic brain tissue, playing certain blood flow compensatory roles.</p>