Studies On The Mechanism Of Reversing Vascular Remodeling By Regulating The Function Of Liver And Kidney And Removing Sputum And Blood Stasis Therapy And Formula

Part One Theory Studies1. Vascular remodeling (VR) and Essential hypertension (EH)Blood vessal exet important regulate function on blood pressure. It canproduce many vasoactive substance and regulate the structure andfunction. So, it's per se handicap and how to rectify it is an important problemon mechanism and prevention and cure of EH, and rectify the changes on vascularsmooth muscle cell's structure and function is the key of the problem.The changes on vessal's structure and function with EH is called vascularremodeling, including:â‘ vas wall incrassation, especially on middle-level,lead the proportion between wall and cavity increased, the resistance of bloodstream and the reaction to the shrink substance is tone up;â‘¡resistance vasis decreased, especially on dia 12-25μm's vas, and bring a series of functionabnormity with it. Many researches are proved: the changes on vas structurehave the relationship with the hyperplasia and hypertrophy of VSMC. VSMC'sstruction changes and vas wall incrassation have the resembled represent indifferent type hypertension, namely, the result of VSMC growth and vasremodeling.VSMC rely on multi-mode excreting biologic active substance to regulateself growth, such as self- excreting. Platelet-derived growth factor (PDGF)and transforming growth factorβ₁(TGF-β₁) have important effect on theevolution of vas plump. Many experiments have proved calcium, especially themanifold dissociate Ca²⁺ in VSMC, is the ultimately together way of themechanism on EH. When cellular Ca²⁺ concentration increased, Ca²⁺与can combinewith calmodin (CaM) create compound, the latter arose VSMC shrinking through phosphated, and can accelerate express of many cancer gene, such as c-fos,c-myc,c-myb, consequently bring the multiplication and plumped of VSMC.2. The research meaning and overview of reverse vascular remodelingVascular remodeling has the consanguineous relation with manyangiocardiopathy, and it can speed the disease process. Although the mechanismof vascular remodeling is still unknown, but the related study and reversevascular remodeling have become the hot spot in the science of the currentresearch.Now most of the biosynthesis preparation can only aim directly at onepath-link The formula of traditional Chinese medicine have the holo-regulationfunction, so its manifests favorable prospect of implication andexploitation. Our research team have been studying by regulating the functionof liver and kidney and removing sputum and blood stasis therapy and formulato prevent and cure the EH and complication, we found that RR-therapy andformula have the favorable holo-regulation function on EH.Part Two Experimental Studies1. Materials and Methods1.1 HerbsComposition and dosage of RR-formula: raidx rehmanniae preparata 25g,carapax et plastrum testudins 30g (break into pieces,fore-decoct),radixsalviae miltiorrhizae 15g,radix notoginseng 5g,ramulus uncariae cum uncis15g (post-decoct),fructus trichosanthis 15g,radix achyranthis bidentatae15g. The herbs are bought from Guangzhou University of Traditional ChineseMedicine affiliated first hospital TCM pharmacy and appraised as pure crudeherbs by the drug department, The concentration of crude herbs is 1.06g/mlafter being fried and concentrated and preserved in refrigerator at 4centi-degree after being cooled under the common temperature.1.2 The subgroup and administration of rats1.2.1 The study of whole curative effectSpontaneously Hypertensive Rat, offered by Beijing Vitalriver laboratoryanimals limited liability company (certification number:0048303), 12week,grade SPF, male aggregately 17, 250±25g in weight, female aggregately 34,160±25g in weight。According to weight and gender divided into four groups:filial generation 1-4 week administration, filial generation 5-10 week administration, filial generation 1-10 week administration, filial generationmodel group: without any administration.From 6 week, observe blood pressure; till 12weeks, kill all rats, observethickness of vas mid-level and the ratio to cavity,cell's ultrastructure.1.2.2 The mechanism discuss by part from body cultivate VSMCSHR primary VSMCwere cultured by tissue culture method, general methodpreparation RR-formuta pastille serum and normal comparison serum, MTT dyeingfiltrate serum concentration that fit the growth of VSMC. Discuss the mechanismof reverse vascular remodeling from calcium system,PDGF—A and TGF—β₁.2. Results2.1 The influence of RR-formula that administration at different period oftime before invasion reverse vascular remodelingSHR were chosen for our research. From the result we can find: the earlytreatment with RR-therapy and formula depressed the development ofhypertension, show in evidence effect after 6 week; S1-4 and S1-10 group'spressure lower than the other groups at 6week, clue to the effect of "brewmilk", but the drug metabolism dynamics need more research. By cell's shapemeasure, we find that herbs can lessened VSM medial thickness of aortae andreduce intima's injury, S1-10 group is best, S1-4 group take second place.Besides, herbs can ameliorate abnormal ultrastructural signs of VSMC from SHRincluding heterogeneous population of nuclei, swelling of mitochondria and tubular systems as well as decreased Ca²⁺. The result clue on that the earlytreatment has finality meaning to the form and growth on VSMC.2.2 The influence of RR-formula pastille serum to calium system on VSMCWe found that the changes of Ca²⁺ and CaM level are increased with timein each group. In S10 and S12 group, [Ca²⁺]i increased evidently than S1 andS5 group, the result maybe related with growth factor. After use pastille serum,[Ca²⁺]i were all lower than normal comparison serum, the result hint thatpastille serum can lower the [Ca²⁺]i and weaken VSMC multiplication andhypertrophy. Combine with experiment 4, maybe related with rivalry Ca²⁺initiative transfer. The changes of Ca²⁺-ATP activity decreased with time ineach group. Pastille serum in S1,S5 and S10 groups compared with S12 group,Ca²⁺-ATP activity were higher than S12 group significantly. The resultsuggested that Ca²⁺-ATP activity have affinity with EH's occurrence anddevelopment, it's mechanism maybe related with a fall in the concentrationof Ca²⁺.2.3 The influence of RR-formula pastille serum to PDGF-A and TGF-β₁, on VSMCWe found that the express of PDGF-A and TGF-β₁ were higher in S12 and S10grouop than S5 and S1 group significantly. The result clue on:â‘ The highexpression maybe important in VSMC's multiplication and vas disfunction inSHR;â‘¡Pastille serum on different period of time have differentrestrainability, that hint administration in forepart is important.Part Three Conclusions1 The research show that the treatment with RR-therapy and formula on differentperiod of time before invasion can depressed the development of hypertensionin some degrees, and the effect of S1-10group is the best. It partially openedout the feasibility and rationality for clinic thought of formula andadministration.2 RR-formula can lessened VSM medial thickness and ameliorate abnormalultrastructural signs of VSMC from SHR. The result clue on that RR-formulacan reverse vascular remodeling in some degrees and the early treatment hasfinality meaning to the form and growth on VSMC.3 RR-formula pastille serum can decrease [Ca²⁺]i and CaM level, increase theactivity of Ca²⁺-ATP, at the same time, it can up-regulate the expression ofCa²⁺-ATP gene and restrain CaM gene. It clue on that the mechanism maybe related with calcium system.4 RR-formula pastille serum can repression the expression of PDGF-A,TGFβ₁protein, it can repression multiplication of VSMC.