The Treatment Of Tianxiangdan For Coronary Heart Disease And Its Experimental Study Of Myocardial Mitochondrial ATPase, MVC And MVD

Background and significance:The study of clinical and experiment about coronary heart disease has been very deepen at home and abroad. As a research of clinical expression and difference in different district about coronary heart disease, the experts of Traditional of Chinese Medicine and integration of traditional and western medicine accumulated rich experience, at the same time, they established treatment and recipe-medicines suitable for use to the local place. This paper is guided by Professor Zhou Mingxin, inherited the senior experience and academic achievement and accumulated the traditional experience of experts in Xinjiang. Furthermore, it made the above all becomes the clinical and experiment research, so made it more scientific.Objective:To study the Clinical and Experimental date on "Tianxiangdan" which was the representative herbal formulas of Tongbukaixie law, investigate the mechanism of Tianxiangdan in treating coronary heart disease (CHD), and to confirm the effect and mechanism of Tianxiangdan's therapeutic action. Through clinical research, to observe the differentiation of the Syndromes of CHD patients, the frequency and regular pattern of clinical symptoms;to survey the effect of Tianxiangdan in patients with CHD on clinical symptoms,improvement of ECG,Coronary collateral circulation and angiogenesis; the Curative effects of Tianxiangdan in patients with CHD on Myocardial Ischemia, Myocardial Function were Evaluated by Straining rate though ultrasound.In animal experiment, to observe the improvement and Effect of Tianxiangdan on Dog's hemodynamics,MVC,MVD,mitochondrial ATPase activity in Rats with myocardial ischemia, the change on myocardial ultra structure observation. The mechanism of Tianxiangdan in treating CHD was illustrated from Cytology. On the base of this, to proof The Theoretical Origin,Thought foundation,Theoretic Basis,Innovational Development through Analyzing and researching the Tongbukaixie law. This paper was divided three the parts to be researched.Partâ… :Clinical Study of Treating coronary heart disease with Tianxiangdan: Methods: 1. The Frequency Investigation of syndrome type. The subjects was the patients with coronary heart disease during 2003.12～2006.12. Results: in 2215 cases, most of patients were huizhuotanzu type, the patients with Qi deficiency and blood stasis type were the second. The frequency of chest pain, chest distension, the oral cavity peculiar smell, dark-red tongue, greasy fur, abnormality of Stool were the highest in these subjects. 2. Research of the effect of Tianxiangdan in patients with CHD and relationship between clinical symptoms and angiogenesis correlation factor. Methods: 620 patientswith stable coronary heart diseases were randomly divided into two groups: the Therapy group (321cases) and the control group (299 cases). The clinical symptoms, Times of angina pectoris attack, duration of the onset of angina, ECG change and the levels of serum vascular endothelial growth factor (VEGF) and nitric oxide (NO) / oxide nitric synthase (NOS) were observed before and after therapy in two groups. 157 cases with coronary heart disease which were diagnosed by coronary artery angiography were randomly divided into excess-syndrome group and deficiency-syndrome group, and were checked the Curative effect, straining rate and strain rate imaging before and after therapy. Results: the improvement in symptoms such as chest pain, chest distension, short breath, palpitation, fatigue,abdominal fullness in two groups were significant different comparing with those before therapy (P<0.01), and the improvement in symptoms such as chest distension, Vertigo,Insomnia, abdominal fullness tongue proper and tongue coating in the Therapy group were statistically significant different comparing with those in the control group too(P<0.05). In two groups, frequency and time of angina pectoris attack, duration of the onset of angina, ECG reading and the levels of serum VEGF and NO/NOS were improved comparing to those before therapy; the Symptoms of deficiency-syndrome group and excess-syndrome group patients were both improved after treating but there were no significant different in two groups (P>0.05), and at different phase in rats, myocardial straining rate in the deficiency-syndrome group and excess-syndrome group were more higher than those before therapy obviously(P<0.01, The result indicated that Tianxiangdan could improve the myocardial ischemia in patients with coronary heart disease and increased the level of VEGF,NO/NOS, Perhaps the Function of Tianxiangdan in treating CHD was related in accelerating angiogenesis, and the Tianxiangdan can both treat the deficiency-syndrome and excess-syndrome types of CHD.Partâ…¡: TianXiangDan's Experimental Study1) The influence of TianXiangDan on the hemodynamics of the anaesthetic dog. Methods: 30 dogs were divided into 5 groups and were monitored the arterial blood pressure, heart rate, left ventricle pressure and coronary blood flow. Results: After given drug 180 minutes, the coronary blood flow of the medicine group with different dose was higher than the blank group. The coronary blood flow in the contrast group and the small, medial, large dose of TianXiangDan group was statistical different compared with the blank group. The large dose of TianXiangDan group was superior to the contrast group, but the difference has no statistical significance. The change of the systolic pressure, the diastolic pressure and the mean blood pressure was not significant different. In given drug 180 minutes, TianXiangDan could elevate the LVSP and LVEDP of the anaesthetic dog with the different degree; It could elevate +dp/dtmax and reduce -dp/dtmax; It also can extend t-dp/dtmax. The difference was statistical significance between treatment group and blank group. The large dose of TianXiangDan group was compared with the contrast group, the discrepancy was statistical significance. It elucidates that TianXiangDan could increase coronary atherosclerotic blood flow through changing the LVSP of the left ventricle systolic pressure and the LVEDP of the end of left ventricle diastolic pressure.2) The effect of TianXiangDan on the ATPase, MVC and MVD of the mitochondria of the big mouse cardiac cell. Methods: 48 big Wistar mice made into the animal model according to the literature were divided into 6 groups. After 6 weeks the mice were killed in order to observe the change of MVC, MVD, the weight of myocardium and the super miniature structure of myocardium, measure the vascular endothelial grow factor and nitrogen monoxide, measure the activeness of the Na+- K +ATPase and Ca2+-Mg2+ATPase of the myocardium mitochondria. Results: The MVC in the treatment group and the small, medial, large dose of TianXiangDan group increase more obviously than the false surgery group and the model group(P<0.05);The MVC and MVD in the medial and large dose of TianXiangDan group increase most remarkably, which was all statistical significance with other groups(P<0.05). The MVC in the small and medial dose group were less than the treatment group, but they all were no statistical significance (P<0.05). The MVD of treatment group increase more obviously than the model group (P<0.05); The MVD of small dose group was between the treatment group and the model group, the discrepancy of three groups was no statistical significance (P<0.05).The NO and the content of VEGF in the treatment group was elevated. The large dose of TianXiangDan group was compared with the contrast group, the discrepancy has statistical significance (P<0.01).The observation of the electrical mirror: The small dose of TianXiangDan group: The muscle- silk break, but the structure of sarcomere was clear, the mitochondria was mildly swell, the keel structure was neat, the nuclear matrix of myocardium get empty lightly, the intercalary plate structure was normal. In the large and medial dose of TianXiangDan group the arrangement of the muscle- silk was neat, the length of sarcomere is uniform, the mitochondria was mildly swell, the keel structure was neat and clear, the nucleus was clearly visible, the intercalary plate structure was normal. The activeness of Na⁺-K⁺- ATP and Ca²⁺- Mg²⁺- ATP of big mouse cardiac cell in the model group was lower than normal group, but TianXiangDan had the capability of enhancing and restoring the activeness of ATP. Moreover, its effect was superior to thecontrast group, and it has the certain relation of quantity and effect. The experiment elucidated that TianXiangDan could effectively improve the anaesthetic dog's coronary atherosclerotic blood flow, improve the pressure of left ventricle, maintain the heart output and stabilize the blood pressure; It could promote the number of miniature blood vessel and the density of miniature blood vessel surface increasing which was in the big mouse myocardium to lack blood, elevate the vascular endothelial grow factor, the nitrogen monoxide and the content of compound enzyme of nitrogen monoxide, and promote the new growth of the blood vessel; It could enhance the activeness of ATP, protect the cardiac cell's super miniature structure, particularly protect the mitochondria, then it could improve the energy metabolism of myocardium for lack of blood against the myocardium to lack blood.Partâ…¢TianXiangDan theoretical basis for the treatment of qi in the chest pain:TianXiangDan was the presentation of Tongbukaixie law. Tongbukaixie law was based on the establishment of Zhongjing chest yangweiyinxuan disease theory for inspiration, Xinjiang Regional Climate and lifestyle characteristics of the community induced qi in the chest, "Derrnatopathy all people of chest pain, not merely heart" of the theory of viscera argument based on the medical history and treatment of chest pain as the source for the thought, Tongbukaixie law based on the recognition that the treatment of Xinjiang chest effective rules.Conclusion1) Dialectical type and frequency of symptoms results in 2,215 cases of coronary heart disease showed that Dialectical typing in huizhuotanzu and qixuxueyu major syndromes; with chest pain, gas foul mouth, heart palpitations, abdominal distention, weakness, Tongue dark, greasy moss mainly syndrome.2) Clinical experiments indicated that TianXiangDan could improve clinical symptoms of coronary heart disease and electrocardiogram; improve the collateral circulation to improve angiogenesis related substances, and promote the role of angiogenesis; from the ultrasonic myocardial strain rate and strain rate imaging, TianXiangDan improve myocardial ischemia in patients with coronary heart disease, especially for the deficiency and the treatment of patients had positive role. TianXiangDan five-organs simultaneously, was a result of viscera, imagination and governance, the overall regulation. Traditional Chinese Medicine to challenge permits only to a certain type Differential Treatment of traditional values.3) Animal experiments confirmed that TianXiangDan could effectively improve the anesthetized dog coronary flow and left ventricular pressure, maintain cardiac output and stable blood pressure; rat myocardial infarction and neovascularization few positive staining area ratio, increased vascular growth factor and nitric oxide and nitric oxide synthase, and promote angiogenesis; from the perspective of cytology TianXiangDan protect myocardial ultrastructure and improve ATPase activity, the protection of mitochondria, thereby improving myocardial ischemia on myocardial energy metabolism ischemia.4) TianXiangDan was an effective treatment of coronary heart disease and on behalf of tongbukaixie. Its formation was based on the false chest superficiality of the disease and the incidence of chest and geographical features of the Xinjiang. Tongbukaixie repair the spirit of the heart lung spleen and kidney, transfer Precious Blood, of phlegm to foul and dirty, bleeding to San Stagnated Yang.5) Tongbukaixie law based on opening Pathogenesis conditions. TianXiangDan treatment of coronary heart disease based on both theory and practice, enriched and developed the theories of diagnosis and treatment of coronary heart disease, the specific application of practical effect, for the treatment of coronary artery disease in theoretical study and practice is of great realistic significance.