Professor Wu Shengyuan 's Academic Thought Of Treating Gout And Anti - Inflammatory Effect And Mechanism Of Modified

Research purposesTo retrace the origin of the fifth national old Chinese medicine expert Professor Wu Sheng Yuan’s academic thought, to learn the academic thoughts of Wu school, to summarize the academic experience of Prof. Wu’s way of treating gout; meanwhile to research the anti-inflammatory mechanism of modified Zhuye Shigao decoction for treating gout, to lay the clinical, theoretical and experimental basis for digging out and developing the advantages of treating this disease by Chinese medicine. At same time starting from the experimental research, to support Professor Wu’s academic thoughts by applying clinically with effective mechanism.Research methodsThere are two main methods: one is to study the ancient Chinese medicine books and follow the teacher clinically, that is to say "Studying Classics, following masters, practicing clinically"; the other is to use cell-mediated immunity, molecular biology and pathology methods to research experimentally the modified Zhuye Shigao decoction.Research contentPart one: Studying and summarizing Professor Wu’s academic thinking and experience in identifying and treating gout.Further to study the Chinese classics and ancient physicians, such as Li Zhongzi, Chen Xiuyuan, Zheng Qinan and Wu Peiheng, to organize the academic heritages, to understand more profoundly of Wu school’s feature and to be beneficial to inherit the academic thought of the school; the clinical experience by following the master and to summarize the academic experience by treating gout from the teacher.Part two: The anti-inflammatory effects and mechanism of modified Zhuye Shigao decoctionOn the research topic "Research on the mechanism of modified Zhuye Shigao decoction conducting IL-1 signal pathway for inhibiting gouty arthritis"(project of Yunnan Provincial Science and Technology Department, NO: 2011FZ262), we detected anti-inflammatory effects of modified Zhuye Shigao decoction on mice of peritonitis model by inducing sodium urate crystal, gouty arthritis model and mononuclear cell models, to discover the possible control mechanism of modified Zhuye Shigao decoction median IL-1 signal pathway.Research conclusionPart one: Professor Wu’s academic thought in identifying and treating goutProfessor Wu inherits, develops and innovates the Wu school academic thoughts, profoundly studies Chinese classics and form his own academic thinking. He has rich clinical experiences and is specialized in using classic prescriptions to treat difficult problems; meanwhile looking into the root of the problem, supporting the upright Qi and eliminating the pathological factors. He puts emphasis on clinical research of TCM, studying both Chinese and Western medicine and has a unique experience in diagnosing and treating gout.1 History of Wu style academic schoolTo retrace the physicians like Li Zhongzi, Chen Xiuyuan, Zheng Qinan and Wu Peiheng’s academic thoughts, they are all derived from the classics of "Yellow Emperor" and "Discussion on Shanghan" and so on. Their thoughts are both inherited and innovated. Physiologically they pay attention to the relationship between yin and yang, fire and water, “The base of Yin and Yang is balance”, the mechanism of water and fire is to support each other; pathologically consider if the dynamic balance of "Yin Yang in harmony", will cause "the separation of yin and yang" to result in "yin or yang symptoms". The treatment focuses on reviving the Yang Qi, tonifying Yang is more important than nourishing Yin, but also follows the principles of identifying patterns and treatment, not to forget "keeping body fluids", by nourishing Yin to control Yang; for heat syndromes should apply supporting Yin and clearing heat, use the way when should be applied. Professor Wu thinks the etiology and pathogenesis of gout has three main points: firstly damp heat and Yin deficiency combine to form the disease. It is often caused by Yin liquid deficiency and not running smoothly. Yin liquid deficiency prone to produce heat and even result in fire, then it burns more body fluid or changes liquid into the sputum; or body fluid’s transporting is blocked and turned into dampness. Phlegm and dampness are both belong to the metabolites and combined together becoming pathogenic factors. They can form stasis at the joints and cause gout; if the stasis lasts a long time it will become tophi. External pathology is often caused by dampness, if it is blocked for a long time it can transform into heat and form damp heat to block the meridians and joints, result in Qi and blood stasis, thus cause pain and give rise to gout. Secondly, people who often consume rich food and alcohol are prone to form damp heat internally and led to gout. If dampness blocked in the middle burner, it’s easy to produce pathogenic cold, if cold and dampness block for a long time they can turn into phlegm and stasis and both become pathogenic factors; if dampness blocks for a long time it turn into heat and flows to the four limbs, thus trig the phlegm and other hidden pathogenic factors to block the Qi blood and meridians and lead to gout, so the pattern is identified as internally cold and externally heat. Thirdly, if the patients have congenital deficiency, liver and kidney deficiency, Jing and blood deficiency, so the bones, tendons and meridians are lack of nourishment; or external symptoms can influence the internal organs, when gout lasts a long time it will damage live, spleen and kidney, in the other hand liver, spleen and kidney disease can also cause gout. Yin deficiency manifests liver and kidney deficiency, Yang deficiency manifests spleen and kidney deficiency, both cause the imbalance of transformation of Qi blood and body fluid and lead to the reoccurrence of gout.2.2 diagnosis and treatment of gout Professor Wu divides the diagnosis and treatment into three stages:(1) acute period: the identified patterns are damp heat accumulation, internal cold and external heat;(2) the interval period: dominated by spleen deficiency and dampness;(3) chronic period: the main patterns are cold dampness blockage, phlegm stasis blockage, liver kidney deficiency, spleen kidney Yang deficiency. Analysis of the feature of the teacher’s diagnosis and treatment of gout :(1) creates the pattern of internal cold and external heat; it is manifested as patients have joints pain, hot when touching the local but no obvious heat in the patient’s body and self feeling chill, prefer warm drinks and so on. It is treated with elimination of both cold and heat, internally and externally. 2 Professor Wu’s academic experience of identifying and treating gout 2.1 Analysis of etiology and pathogenesis of gout Internally he eliminates the cold and dampness, warms the meridians and makes Qi flowing free; externally he clears the heat and detoxifies, removes stasis and dissipate swelling. Internally taking prescription of Huangqi Fangji decoction, externally using Kusheng Huangbai decoction to wash(later he made the hospital preparation "gout eliminating and washing composition" both for taking internally and washing externally and applied clinically for more than 10 years). In 2001 my teacher personally put "gout elimination" combination into pharmacodynamic tests and proved its effectiveness and safety.(2) Pattern of heat and dampness accumulation: actually it contains both heat and Yin deficiency mechanism, should be treated with clearing heat, eliminating dampness, nourishing Yin and making free flow of meridians; applied with prescription of modified Zhuye Shigao decoction, in order to clear heat dampness and nourish yin at same time. In this way the symptoms and the root are both treated, the pathogenic factors are eliminated without injuring the upright Qi, the upright Qi is tonified without retaining the pathogenic factors, so the principles, methods, prescriptions and herbs are applied completely, it is my teacher’s unique way of treatment. In the beginning stage lots of clinical observations and researches were done and proved to be effective, on this basis the experimental studies were carried out and further research from the molecular biology point of view to see its possible mechanism. In the chronic period the major patterns are spleen and kidney yang deficiency, liver and kidney deficiency, reflecting the master’s academic thought of looking into the root when treating diseases.Part two:Study of anti-inflammatory effects and mechanism of modified Zhuye Shigao decoctionExperiment one1. Serum IL-1βand Caspase-1 of gouty arthritis mode in mice were significantly increased compared with the model group, while serum IL-1βand Caspase-1 of mice with modified Zhuye Shigao decoction group were lower(P﹤0.05); meanwhile, modified Zhuye Shigao decoction can lower the gouty arthritis indicating data respectively, the pathology results show that it can reduce the inflammatory cell infiltration and significantly improve the symptoms of arthritis in mice.2. Serum IL-1β and Caspase-1 of the mice group with peritonitis mode significantly increased; compared with the model group, serum IL-1β and Caspase-1 of mice groups with high, medium and low dosage of modified Zhuye Shigao decoction are lower(P﹤0.05); compared with the group mode of positive drug colchicine, serum IL-1β and Caspase-1 of the mice group with high dosage of modified Zhuye Shigao decoction are also lower(P﹤0.05).Experiment two1. Through the analysis of intervention of modified Zhuye Shigao decoction serum containing the optimum concentration of THP-1 cells, 10% of modified Zhuye Shigao decoction containing drug serum concentration is a suitable concentration, can be used for subsequent protein expressing analysis.2. By western blot detection, if compared with normal standard group with same concentration, in modified Zhuye Shigao decoction containing drug serum, the protein level of Pro-IL-1 and Pro-caspase-1 of the group with high dosage were significantly decreasing.3. By ELISA assay, if compared with normal standard group, IL-1 and IL-18 concentrations of model group were significantly increased; After the intervention of modified Zhuye Shigao decoction containing drug serum, IL-1 and IL-18 concentrations have trends of decreasing. Compared with the model group, IL-1 and IL-18 of mice group with high dosage of modified Zhuye Shigao decoction were significantly decreased(P﹤0.05).Through experimental study, it revealed the modified Zhuye Shigao decoction may go through interleukin signal pathway to involve in the process of the mode of inflammation evolution by lower interleukin-inflammatory factors. It fills the gaps in the prescription experimental study, provides a theoretical basis for the treatment of gout and enriches the theory of Chinese medicine for the prevention of gout.