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Hypertension Pathogenesis And Grass Buck Soup Antihypertensive Effect And Mechanism,

Posted on:2008-05-02Degree:DoctorType:Dissertation
Country:ChinaCandidate:R B QuFull Text:PDF
GTID:1114360212988909Subject:TCM clinical basis
Abstract/Summary:PDF Full Text Request
Hypertension is a familiar chronic cardiovascular disease. Not only the incidence of hypertension is high, moreover, the course of the diseases is comparatively longer, its pathology mechanism is complex. This syndrome has many complications, that ofen associates with the damage of important viscera such as heart, brain, kidney and so on, which threatens the health of human being seriously. So the research on the pathogenesis of hypertension and curatives is one of the hotspots of international medical field all over the world. More and more proofs make it clear that T.C.M. has unique advantage on the therapy of hypertension and some available prescriptions have been accumulated in the long-term clinic practices. Reduction analysis of the pathology characteristics of hypertension, comprehensive evaluation the curative effect of clinic effective prescriptions, clarification the mechanism in treating , to study its mechanism in treating essential hypertension, thus development new therapy medicine of hypertension and providing more effective trerapy methods for clinic are important contents of modernization of T.C.M..Pathogenesis possesses very important postion in T.C.M. theory. This study discussed pathogenesis of essential hypertension respectively according to different levels, then probed into the relationship of various levels in order to ascertain the skeleton venation of pathogenesis system.San Cao Jiang Ya Tang (SCD) is an experience prescription formulated by famous old doctor of Chinese medicine Liu Du-zhou, a professor of our uviversity, the prescription has been proofed effective in treating hypertension. In this study we maked use of modern pharmacology, comprehensively evaluates this prescription's effect on hypertension and clarifies its mechanism on therapy of hypertension so as to establish modern research foundation for the development and application of this prescription.Only through foundmental and applied experiment research by using"animal model with combined syndromes and symptoms", can the research results reveal the scientific meanings of T.C.M. theories such as treatment based on syndrome differentiation, prescriptions corresponding to syndromes and so on, representing the characterisctis and advantages of traditional chinese medicine. This study comprehensively researched symptom attributes of the spontaneously hypertensive rat (SHR) and the renal hypertensive rat (RHR), providing new thinking on setting up modern animal models for T.C.M. researches.Objective 1 Discuss the mechanism of hypertension and SCD's prescription theory in treating hypertension;2 Evaluate SCD's effect in treating hypertension;3 Clarify SCD's mechanism in treating hypertension;4 Differentiate Syndrome attributes between SHR and RHR elementarily.Methods1 Theoretics researchSystemically discuss the pathogenesis of hypertension through organizing literatures about it.Preliminary analysis the prescription theory of SCD based on maladjustment pathogenesis of Qi, blood and vessel in hypertension.2 Experiment researchSHR and two-kindy, one clip (2K1C) RHR were used as animal model. Tail-artery blood pressure measurement for conscious rats was used to observe the time-effect, dose-effect and long-term treatment features of the medicine to the blood pressure of the rats.The effect of SCD to animal model was studied by observeing macro representations and behavior. The blood pressure regulating factors in the plasma was examined by the method of radioimmunoassay and biochemistry. The target-organ damage was observed by pathologic slices making.Result1 Theoretics researchPathogenesis of hypertension can be divided into several different levels, such as basic pathogenesis, pathogenesis of representation, pathogenesis of disease, pathogenesis of syndromes, and micro pathogenesis. Maladjustment between Qi and blood and obstruct of the vessels are the key to the pathology mechanism of this disease. Prescription characteristics of SCD lies in that it can concurrently cure Qi, blood and vessels.2 Experiment research2.1 Research on SCD's therapy on hypertension of SHR and mechanism(1) The time-effect and dose-effect study of one time treatment of SCD showed that, the time-effect feature of low, middle, high comcentration were similar, they all got the maximum antihypertensive effect at 4h after drug taken, then the blood pressure began to rise, and got back to the level before drug taken at 8h. The dose-effect study shows, the middle, high comcentration groups all had their blood pressure droped obviously at 4h aftert drug taken (p < 0.01), the blood pressure droped about 10mmHg, the low comcentration had no obvious antihypertensive effect.(2) Between 14-18 week-age, compared with the normal group, the SHR model group's blood pressure was higher (p<0.01), heart rate was higher (p<0.01), irritable degree was higher (p<0.05 or p<0.01), pain threshold was higher (p<0.01), time persisting on rotary table was shorter (p<0.05 or p<0.01), eyes pop degree was higher (p<0.01), body weight was obviously lower at 18 week-age (p<0.05), and they looked more tentional, often fight between the cagemates, their hair color was more yellow, lacklusterits and losing more, their urine was more yellow, their dejection was more dry. In the 4 weeks treatment, compared with the model group, the SCD group's blood pressure droped obviously (p<0.01), heart rate and pain threshold had no obvious change, irritable degree reduced (p<0.01), time persisting on rotary table extended (p<0.05), eye pop degree and body weight had no obvious chang, tension and fight reduced, urine color was ligter, dejection was wetter.(3) Pathomorphology shows, the transverse diameter of ventricular myocyte turned thicker; glomerular sclerosis, atrophy and centralize could be seen in some part of cortex of rats kidney, lymphocytic infiltration could be seen in thestromal; nerve cell addiction and encephalomalacia phenomenon could be seen in some part of the pallium. After 4 weeks treatment, the phenomena above were less in SCD group.(4) Compared with normal group, both heart weight index and left ventricular mass index of SHR model group inceased (p<0.01), blood plasma AngII level was lower (p<0.01), ET increased (p<0.01), ANP reduced (p<0.01), contents of PRA,CGRP,NO had no obvious differences.After 4 weeks treatment, compared with model group, the heart weight index and left ventricular mass index had no obvious difference, blood plasma ET level reduced (p<0.01), ANP hoisted (p<0.01), NO hoisted (p<0.01), AngII,PRA,CGRP had no obvious change.2.2 Research on SCD's therapy on hypertension of RHR and mechanism(1) Time-effect study of one time treatment of SCD showed that, the time-effect feature of low, middle, high comcentration were similar, they all got the maximum antihypertensive effect at 4h after drug taken, then the blood pressure began to rise, and got back to the level before drug taken at 8h. The dose-effect study shows, the low, middle, high comcentration groups all had their blood pressure droped obviously 4h aftert drug taken (p<0.05 or p<0.01), the middle comcentration group's blood pressure droped about 17mmHg, the high comcentration group's droped 10mmHg, and the low comcentration group's droped 6mmHg. (2) Compared with the normal group, the RHR model group's blood pressure was higher (p<0.01), heart rate was higher (p<0.05 or p<0.01), pain threshold was higher (p<0.05), body weight was obviously lower at 18 weeks age (p<0.01), and it had lower spirits, its hair color was lackluster, its urine was more lighter-colored, it was enuresis being holded up, its dejection was more wet, and had a heavier moldy smell.In the 4 weeks being treated, compared with the model group, the SCD group's blood pressure droped obviously (p<0.01), heart rate reduced, body weight hoisted, pain threshold hoisted, time persisting on rotary table extended, and the hair color and enuresis got better.(3) Pathomorphology shows, the transverse diameter of ventricular myocyte turned thicker; glomerular sclerosis, atrophy and centralize in some part of cortex of rats kidney, lymphocytic infiltration in thestromal and hyaline changes in the artery beside the glomerular could be seen; nerve cell addiction and encephalomalacia phenomenon can be seen in some part of the pallium. After 4 weeks treatment, the phenomena above were less in SCD group.(4) Compared with normal group, both heart weight index and left ventricular mass index of RHR model group inceased (p<0.01), blood plasma PRA level increased (p<0.01), AngII inctreased (p<0.05), ANP increased (p<0.01), contents of ET, CGRP, NO had no obvious differences.After 4 weeks treatment, compared with model group, the heart index and left ventricle had no obvious difference, blood plasma PRA level reduced (p<0.01), AngII reduced (p<0.05), ET reduced and NO hoisted (p<0.01), ANP, CGRP had no obvious change.2.3 Study on individual differences of blood pressure response of SHRs to SCD Although blood pressure decreased obviously in many individuals, there was no obvious difference in the blood pressure of 29% SHR after taken SCD. When the dose was increased or decreased, blood pressure of these insensitive rats still didn't improve. Conclusion1 Maladjustment between Qi and blood and obstruct of the vessels are key factors of hypertension pathogenesis. Therapy on Qi,blood and vessels concurrently is SCD'S prescription characteristics;2 SCD has obvious effect on therapy of hypertension and the effect can last 6 hours, furthermore, its dosage and effect have some relativity;3 SCD can improve SHR and RHR's syndrome, which shows its holistic therapy effects;4 the study illustrates SCD's mechanism on the therapy of Hypertension mechanism elementarily and finds SCD has different operation mechanism on two hypertension models;5 In early stage of the disease, SHR'reaction on treatment of hypertension has individual difference.
Keywords/Search Tags:Hypertension, San Cao Jiang Ya Tang, Pathogenesis, Antihypertensive, Pharmacology Mechanism
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